• Long-term glaucoma surveillance and IOP management of both eyes.
A. Immediate medical therapy to lower IOP
1. Systemic hyperosmotic agents are required initially if IOP is more than 40 mm Hg.
• Intravenous mannitol (1 gm/kg body weight) should be preferred in the presence of nausea and vomiting.
• Oral hyperosmotics, e.g., glycerol 1 gm/kg body weight of 50% solution in lemon juice may be given if well tolerated and not contraindicated (as in diabetes mellitus).
2. Systemic carbonic anhydrase inhibitors, e.g., acetazolamide 500 mg IV stat followed by 250 mg tablet 3 times a day.
3. Topical antiglaucoma drugs to be instilled immediately include:
• Beta-blocker, e.g., 0.5% timolol or 0.5% betaxolol • Alpha adrenergic agonists, e.g., brimonidine
0.1–0.2%.
• Prostaglandin analogue, e.g., latanoprost 0.005%. Role of miotic therapy:
• Pilocarpine 2% QID should be started after 1 hour of the commencement of the treatment, i.e., when IOP is lowered, as at higher IOP sphincter is ischaemic and unresponsive to pilocarpine.
Note. Intensive miotic therapy is not advised nowadays. Some glaucoma experts have given up the use of pilocarpine entirely in the management of acute PACG.
4. Analgesics and antiemetics may be required to alleviate the symptoms.
5. Compressive gonioscopy with a 4 mirror goniolens may help relieve pupil block and is essential to determine if the trabecular blockage is reversible. 6. Topical steroid, e.g., prednisolone acetate 1% or dexamethasone eye drops administered 3–4 times a day reduces the inflammation.
B. Definitive therapy
1. Laser peripheral iridotomy (LPI). Gonioscopy should be performed as soon as cornea becomes clear. Laser PI should be performed if PAS are seen in <270° angle. LPI re-establishes communication between posterior and anterior chamber, so it bypasses the pupillary block and immediately relieves the crowding of the angle.
• Laser peripheral  iridotomy (with Nd:YAG laser or Argon Laser) should always be preferred over surgical PI. However, if lasers are not available surgical PI should be done (see page 253 for technique).
2. Filtration surgery, i.e., trabeculectomy should
246	Section III   Diseases of Eye


be performed in cases where IOP is not controlled with the maximum medical therapy following an attack of acute PAC or when gonioscopy reveals PAS >270° angle and also when peripheral iridotomy is not effective.
• Mechanism: Filtration surgery provides an alternative to the angle for drainage of aqueous from anterior chamber into subconjunctival space. Surgical technique. (see page 254).
3. Clear lens extraction by phacoemulsification with intraocular lens implantation has recently been recommended by some workers, especially in the presence of phacomorphic etiology (diagnosed on UBM).
C. Prophylactic treatment in the normal fellow eye Prophylactic laser iridotomy (preferably) or surgical peripheral iridectomy should be performed on the fellow asymptomatic eye (PACS) as early as possible as chances of acute attack are 50% in such eyes.
D. Long-term glaucoma surveillance and IOP man-agement in both eyes
Long-term glaucoma surveillance and IOP management in both eyes of a patient with acute PAC is must to ultimately prevent glaucomatous blindness: ■Eyes treated with PI (both affected and fellow eye) may develop PACG at any time. So, it should be treated as and when required.
■Filtration surgery may fail anytime during the course and hence need to be repeated with antimetabolites.
Sequelae of acute PAC
Clinical status of the eye after an attack of acute PAC with or without treatment is considered a sequelae of acute PAC. It may be seen as following clinical settings: 1. Postsurgical acute PAC. This refers to the clinical status of the eye after laser peripheral iridotomy (PI) treatment for an attack of acute PAC. It may occur in two clinical settings:
i.  With normalized IOP after successful laser PI, the eye usually quitens after sometime with or without marks of an acute attack (i.e., Vogt’s triad, see below).
ii. With raised IOP after unsuccessful laser PI, which needs to be treated by trabeculectomy operation.
2. Spontaneous angle reopening may occur very rarely in some cases and the attack of acute PAC may subside itself without treatment.
Treatment of   choice for such cases is laser peripheral iridotomy.
3. Ciliary body shut down. It refers to temporary cessation of aqueous humour secretion due to ischaemic damage to the ciliary epithelium after an attack of acute PAC.

Clinical features in this stage are similar to acute PAC except that the IOP is low and pain is markedly reduced. Subsequent recovery of ciliary function may lead to chronic elevation of IOP with cupping and visual field defects, i.e., PACG.

Treatment includes:
• Topical steroid drops to reduce inflammation.
• Laser peripheral iridotomy should be performed when cornea becomes clear and IOP should be monitored.
• Trabeculectomy is required when IOP rises constantly.
4. Vogt’s triad. It may be seen in both treated and non-treated cases after an attack of acute PAC. It is characterized by:
• Glaukomflecken (anterior subcapsular lenticular opacity),
• Patches of iris atrophy, and
• Slightly dilated nonreacting pupil (due to sphincter atrophy).

III. Primary Angle-Closure Glaucoma Primary angle closure glaucoma (PACG) can be considered analogous to the term ‘chronic primary angle closure glaucoma’ used in the clinical classification.
Pathogenesis
Primary angle-closure glaucoma (PACG) results from gradual synechial closure of the angle of anterior chamber. Untreated patients with PAC may over the period covert to PACG with or without history of subacute or acute attack of PAC.
Clinical features
PACG may clinically manifest as subacute, acute or chronic PACG.
Subacute and acute PACG clinically present as similar to subacute  and acute PAC, respectively (see page 244); except that glaucomatous optic disc changes and visual field defects are always present in PACG.
Chronic PACG. Clinical features, given below, are similar to POAG except that angle closure is present: ■Intraocular pressure (IOP) remains constantly raised.
■Eyeballremains white (no congestion) and painless, except in post acute angle closure cases where the eye may be congested and irritable.
■Optic disc shows glaucomatous cupping.
■Visual field defects similar to POAG occur (see page 232).
■Gonioscopy reveals more than 270° of angle closure along with peripheral anterior synechiae (PAS). The
Chapter 10	Glaucoma	247


gonioscopic findings provide the only differentiating feature between POAG and chronic PACG.
Diagnosis
Defining criteria for primary angle closure glaucoma (PACG) as per ISGEO classification is:
• Irido-trabecular contact is noted on gonioscopy in greater than 270° of angle,
• PAS are formed, • IOP is elevated,
• Optic disc shows glaucomatous damage, and
• Visual fields show typical glaucomatous defects.
Impression: Angle is abnormal in function (elevated IOP) and structure (PAS + ve) with optic neuropathy. Note. In circumstances where advanced PACG disease with compromised media prohibits disc and visual field testing, e.g., cataract or corneal disease, a coarser definition holds for PACG whereby an IOP > 24 mm Hg and visual acuity of < 3/60 or a history of prior glaucoma surgery, will suffice.
Treatment
• Laser iridotomy alone or alongwith medical therapy similar to POAG (see page 236) should be tried first.
• Trabeculectomy (filtration surgery) is needed when the above treatment fails to control IOP.
• Prophylactic laser iridotomy in fellow eye must also be performed.

Absolute Primary Angle-closure Glaucoma Primary angle closure glaucoma, if untreated, gradually passes into the final phase of absolute glaucoma.
Clinical features
• Painful blind eye. The eye is painful, irritable and completely blind (no light perception).
• Perilimbal reddish blue zone, i.e., a slight ciliary flush around the cornea due to dilated anterior ciliary veins.
• Caput medusae, i.e., a few prominent and enlarged vessels are seen in long-standing cases.
• Cornea in early cases is clear but insensitive. Slowly it becomes hazy and may develop epithelial bullae (bullous keratopathy) or filaments (filamentary keratitis).
• Anterior chamber is very shallow. • Iris becomes atrophic.
• Pupil becomes fixed and dilated and gives a greenish hue.
• Optic disc shows glaucomatous optic atrophy.
• Intraocular pressure is high; eyeball becomes stony hard.


Management of absolute glaucoma
1. Retrobulbar alcohol injection: It may be given to relieve pain. First, 1 ml of 2% xylocaine is injected followed after about 5–10 minutes by 1 ml of 80% alcohol. It destroys the ciliary ganglion.
2. Destruction of secretory ciliary epithelium to lower the IOP may be carried out by cyclocryotherapy(seepage 256) or cyclodiathermy or cyclophotocoagulation.
3. Enucleation of eyeball. It may be considered when pain is not relieved by conservative methods. The frequency with which a painful blind eye with high IOP contains a malignant growth, justifies its removal. (For surgical technique of enucleation see page 308).
Complications
Absolute glaucoma, if not treated, following complications may occur due to prolonged high IOP: Corneal ulceration.It results from prolonged epithelial oedema and insensitivity. Sometimes, corneal ulcer may even perforate.
Staphyloma formation. As a result of continued high IOP, sclera becomes very thin and atrophic and ultimately bulges out either in the ciliary region (ciliary staphyloma) or equatorial region (equatorial staphyloma).
Atrophic bulbi. Ultimately  the  ciliary  body degenerates, IOP falls and the eyeball shrinks.

SECONDARY GLAUCOMAS

Secondary glaucoma per se is not a disease entity, but a group of disorders in which rise of intraocular pressure is associated with some primary ocular or systemic disease. Therefore, clinical features comprise that of primary disease and that due to effects of raised intraocular pressure.
Classification

A. Depending upon the mechanism of rise in IOP
1. Secondary open angle glaucomas in which aqueous outflow may be blocked by:
• Pretrabecular membrane, • Trabecular clogging,
• Oedema and scarring or
• Post-trabecular elevated episcleral venous pressure.
2. Secondary angle closure glaucomas which may or may not be associated with pupil block.
B. Depending upon the causative primary disease, secondary glaucomas are named as follows:
1. Lens-induced (phacogenic) glaucomas.
2. Inflammatory glaucoma (glaucoma due to intraocular inflammation).
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3. Pigmentary glaucoma. 4. Neovascular glaucoma.
5. Glaucomas associated with iridocorneal endothelial syndromes.
6. Pseudoexfoliative glaucoma.
7. Glaucomas  associated  with  intraocular haemorrhage.
8. Steroid-induced glaucoma. 9. Traumatic glaucoma.
10. Glaucoma-in-aphakia.
11. Glaucoma associated with intraocular tumours.

LENS-INDUCED (PHACOGENIC) GLAUCOMAS In this group IOP is raised secondary to some disorder of the crystalline lens. Lens induced glaucoma can be classified as below:
Lens-induced secondary angle closure glaucoma • Phacomorphic glaucoma (due to swollen lens)
• Phacotopic glaucoma (due to anterior lens displacement).
Lens-induced secondary open angle glaucoma • Phacolytic glaucoma
• Lens particle glaucoma
• Phacoanaphylactic glaucoma.

1. Phacomorphic Glaucoma
Causes. Phacomorphic glaucoma is an acute secondary angle-closure glaucoma caused by: ■Intumescent lensi.e., swollen cataractous lens due to rapid maturation of cataract or sometimes following traumatic rupture of capsule is the main cause of phacomorphic glaucoma.
■Anterior subluxation or dislocation of the lens and spherophakia (congenital small spherical lens) are causes of phacotopic (a variant of phacomorphic) glaucoma.
Pathogenesis. The swollen lens pushes the iris forward and oblitrates the angle resulting in secondary acute angle closure glaucoma. Further, the increased iridolenticular contact also causes potential pupillary block and iris bombe formation.
Clinical presentation. Phacomorphic glaucoma presents as acute congestive glaucoma with features almost similar to acute primary angle-closure (see page 244) except that the lens is always cataractous and swollen (Fig. 10.21). Demonstration of deep anterior chamber and open angle in the fellow eye helps in differentiating from the acute primary angle closure glaucoma.
Treatment should be immediate and consists of:
• Medical treatment to control IOP by IV mannitol, systemic acetazolamide and topical beta-blockers.

















Fig. 10.21 Phacomorphic glaucoma. Note ciliary congestion, dilated pupil and intumescent senile cataractous lens
• Laser iridotomy may be effective in breaking the angle-closure attack.
• Cataract extraction with implantation of PCIOL (which is the main treatment of phacomorphic glaucoma) should be performed once the eye becomes quiet.

2. Phacolytic Glaucoma (Lens Protein Glaucoma)
Pathogenesis. It is a type of secondary open angle glaucoma, in which trabecular meshwork is clogged by the lens proteins, macrophages which have phagocytosed the lens proteins, and inflammatory debris. Leakage of the lens proteins occurs through an intact capsule in the hypermature (Morgagnian) cataractous lens.
Clinical features. The condition is characterised by: • Features of  acute congestive glaucoma (see page
244) due to an acute rise of IOP in an eye having hypermature cataract.
• Anterior chamber may become deep and aqueous may contain fine white protein particles, which settle down as pseudohypopyon.
• Anterior chamber angle is open on gonioscopy.

Management consists of:
• Medical therapy to lower the IOP (see page 236) followed by
• Extraction of the hypermature cataractous lens with PCIOL implantation.

3. Lens Particle Glaucoma
Pathogenesis. It is a type of secondary open angle glaucoma, in which trabecular meshwork is blocked
Chapter 10	Glaucoma	249


by the lens particles floating in the aqueous humour. It may occur due to lens particles left after accidental or planned extracapsular cataract extraction or following traumatic rupture of the lens.
Clinical features. Symptoms of acute rise in IOP (see page 243) associated with lens particles in the anterior chamber.
Management includes:
• Medical therapy to lower IOP (see page 236) and • Irrigation-aspiration of the lens particles from the
anterior chamber.

4. Phacoantigenic Glaucoma
In this condition, there occurs fulminating acute inflammatory reaction due to antigen (lens protein)—antibody reaction. The mechanism of rise in IOP and its management is similar to that of acute inflammatory glaucoma. Typical finding is a granulomatous inflammation in the involved eye after it goes surgical trauma.
Pathogenesis. As in the case of lens particle glaucoma, there is usually a preceding disruption of lens capsule by extracapsular cataract extraction, penetrating injury, or leak of proteins from the capsule. Distinguishing feature is a latent period during which sensitization to the lens proteins occurs. IOP is then raised due to inflammatory reaction of the uveal tissue excited by the lens matter. Basically, it is also a type of secondary open angle glaucoma where trabecular meshwork is clogged by both inflammatory cells and the lens particles.
Management consists of:
• Medical therapy to lower IOP,
• Treatment of iridocyclitis with steroids and cycloplegics.
• Irrigation-aspiration of the lens matter from anterior chamber (if required) should always be done after proper control of inflammation.

GLAUCOMAS DUE TO UVEITIS
The IOP can be raised by varied mechanisms in inflammations of the uveal tissue (iridocyclitis). Even in other ocular inflammations such as keratitis and scleritis, the rise in IOP is usually due to secondary involvement of the anterior uveal tract.
Types
I. Non-specific inflammatory glaucomas, and II. Specific hypertensive uveitis syndromes.

I. Non-Specific Inflammatory Glaucoma Based on the mechanism of rise in IOP the inflammatory glaucoma can be:

• Open-angle inflammatory glaucoma, and • Angle-closure inflammatory glaucoma.
1. Open-angle inflammatory glaucoma
Clinically, the open-angle inflammatory glaucoma may manifest as acute or chronic entity.
i. Acute open-angle inflammatory glaucoma Mechanisms of rise in IOP. The acute open-angle glaucoma occurs due to trabecular clogging (by inflammatory cells, exudates and turbid aqueous humour), trabecular oedema (due to associated trabeculitis), and prostaglandin-induced rise in IOP. Clinical features. It is characterized by features of acute iridocyclitis associated with raised IOP with open-angle of anterior chamber. IOP usually returns to normal after the acute episode of inflammation. Management. It includes treatment of iridocyclitis and medical therapy to lower IOP by use of hyperosmotic agents, acetazolamide and beta-blocker eye drops (timolol or betaxolol).
ii. Chronic open angle inflammatory glaucoma Mechanism of rise in IOP includes chronic trabeculitis, and trabecular scarring.
Clinical features include raised IOP, open angle, no active inflammation but signs of previous episode of uveitis are often present. Some chronic cases may also have signs of glaucomatous disc changes and field defects.
Treatment consist of:
■Medical therapy with topical beta-blockers, and/ or carbonic anhydrase inhibitors and alpha agonist may be useful. Preferably avoid pilocarpine and prostaglandin agonists.
■Trabeculectomy, under cover of steroids, may be tried, if medical treatment fails. The results are usually poorer than POAG, but can be improved by augmented trabeculectomy or tube procedures. ■Cyclodestructive procedures (e.g. cyclodiode) may need to be considered if surgical treatment fails.
2. Angle-closure inflammatory glaucoma
When uveitis is not treated, over the period PAS are formed causing synechiae angle closure.
Mechanisms of rise in IOP include:
■Secondary angle-closure with pupil block. Pupillary block due to annular synechiae or occlusio pupillae leads to iris bombe formation followed by angle closure.
■Secondary angle-closure without pupil block occurs due to organisation of the inflammatory debris in the angle, which on contraction pulls the iris over the trabeculum. It is followed by gradual and progressive synechial angle closure with eventual elevation ofIOP.
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Clinical featuresinclude raised IOP, seclusio papillae, iris bombe, shallow anterior chamber.
Management includes prophylaxis and curative treatment.
1.Prophylaxis. Acute iridocyclitis should be treated energetically with local steroids and atropine to prevent formation of synechiae.
2.Curative treatment. It consists of medical therapy to lower IOP (miotics are contraindicated). Surgical or laser iridotomy may be useful in pupil block without angle closure. Filtration surgery may be performed (with guarded results) in the presence of angle closure.

II. Specific Hypertensive Uveitis Syndromes These include:
■Fuchs’ uveitis syndrome (see page 169) and ■Glaucomatocyclitic crisis (see page 169).
PIGMENTARY GLAUCOMA
It is a type of secondary open-angle glaucoma wherein clogging up of the trabecular meshwork occurs by the pigment particles. About 50% of patients with the Pigment dispersion syndrome (PDS) develop glaucoma.
Pathogenesis. Exact mechanism of pigment shedding is not known. It is believed that, perhaps, pigment release is caused by mechanical rubbing of the posterior pigment layer of iris with the zonular fibrils.
Clinical features include:
• Young myopic males typically develop this glaucoma.
• Characteristic glaucomatous features are similar to primary open angle glaucoma (POAG), associated with.
• Deposition of pigment granules in the anterior segment structures such as iris, posterior surface of the cornea (Krukenberg’s spindle), trabecular meshwork, ciliary zonules and the crystalline lens.
• Gonioscopy shows pigment accumulation along the Schwalbe’s line especially inferiorly (Sampaolesi’s line).
• Iris transillumination shows radial slit-like transillumination defects in the mid periphery (pathognomic feature).
Treatment. It is exactly on the lines of primary open angle glaucoma.
NEOVASCULAR GLAUCOMA (NVG)
It is an intractable glaucoma which results due to formation of neovascular membrane involving the angle of anterior chamber.

Etiology. It is usually associated with neov-ascularization of iris (rubeosis iridis). Neov-ascularization develops following retinal ischaemia, which is a common feature of:
• Proliferative diabetic retinopathy, • Central retinal vein occlusion,
• Sickle-cell retinopathy, and • Eales’ disease.
• Other rare causes are chronic intraocular inflammations, intraocular tumours, long-standing retinal detachment and central retinal artery occlusion.
Clinical profile. NVG occurs in three stages:
1.Pre-glaucomatous stage (stage of rubeosis iridis); 2.Open-angle glaucoma stage—due to formation of
a pretrabecular neovascular membrane; and 3.Secondary angle closure glaucoma—due to
goniosynechiae resulting from contracture of the neovascular membrane (zipper angle closure).

Treatment of NVG is usually frustrating, includes:
• Panretinal photocoagulation may be carried out to prevent further neovascularization.
• Medical therapy and conventional filtration surgery are usually not effective in controlling the IOP.
• Glaucoma drainage device, i.e., artificial filtration shunt (Seton operation) may control the IOP.
GLAUCOMA ASSOCIATEDWITH INTRAOCULAR TUMOURS
Secondary glaucoma due to intraocular tumours such as malignant melanoma (of iris, choroid, ciliary body) and retinoblastoma may occur by one or more of the following mechanisms:
• Trabecular block due to clogging by tumour cells or direct invasion by tumour seedlings.
• Neovascularization of the angle.
• Venous stasis following obstruction of the vortex veins.
• Angle closure due to forward displacement of iris-lens diaphragm by increasing tumour mass.

Treatment. Enucleation of the eyeball should be carried out as early as possible.

PSEUDOEXFOLIATIVE GLAUCOMA (GLAUCOMA CAPSULARE)
Pseudoexfoliation syndrome (PES) is characterised by deposition of an amorphous grey dandruff-like material on the pupillary border, anterior lens surface, posterior surface of iris, zonules and ciliary processes.
• Exact source of the exfoliative material is still not known.
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• Secondary open-angle glaucoma is associated in about 50% of the cases.
• Exact mechanism of rise of IOP is also not clear. Trabecular blockage by the exfoliative material is considered as the probable cause.
• Clinically, the glaucoma behaves like POAG and is thus managed on the same lines.
GLAUCOMAS-IN-APHAKIA/PSEUDOPHAKIA It is the term used to replace the old term ‘aphakic glaucoma’. It implies association of glaucoma with aphakia or pseudophakia. It includes following conditions:
1.Raised IOP with deep anterior chamber in early postoperative period. It may be due to hyphaema, inflammation, retained cortical matter or vitreous filling the anterior chamber.
2.Secondary angle-closure glaucoma due to flat anterior chamber. It may occur following long-standing wound leak.
3.Secondary angle-closure glaucoma due to pupil block. It may occur following formation of annular synechiae or vitreous herniation.
4.Undiagnosed pre-existing primary open-angle glaucoma may be associated with aphakia. pseudophakia.
5.Steroid-induced glaucoma. It may develop in patients operated for cataract due to postoperative treatment with steroids.
6.Epithelial ingrowth may cause an intractable glaucoma in late postoperative period by invading the trabeculum and the anterior segment structures.
7.Aphakic/pseudophakic malignant glaucoma (see page 252).
STEROID-INDUCED GLAUCOMA
It is a type of secondary open-angle glaucoma which develops following topical, and sometimes systemic steroid therapy.
Etiopathogenesis. It has been postulated that the response of IOP to steroids is genetically determined. Roughly, 5% of general population is high steroid responder (develop marked rise of IOP after about 6 weeks of steroid therapy), 35% are moderate and 60% are non-responders.
Mechanism responsible for the obstruction to aqueous outflow is unknown. Following theories have been put forward:
■Glycosaminoglycans (GAG) theory. Corticosteroids inhibit the release of hydrolases (by stabilizing lysosomal membrane). Consequently, the GAGs present in the trabecular meshwork cannot depolymerize and they retain water in the

extracellular space. This leads to narrowing of trabecular spaces and decrease in aqueous outflow. ■Endothelial cell theory.Under normal circumstances the endothelial cells lining the trabecular meshwork act as phagocytes and phagocytose the debris from the aqueous humour. Corticosteroids are known to suppress the phagocytic activity of endothelial cells leading to collection of debris in the trabecular meshwork and decreasing the aqueous outflow. ■Prostaglandin theory. Prostaglandin E and F (PGE and PGF) are known to increase the aqueous outflow facility. Corticosteroids can inhibit the synthesis of PGE and PGF leading to decrease in aqueous outflow facility and increase in IOP. Clinical features. Steroid-induced glaucoma typically resembles POAG (see page 229). It usually develops following weeks of topical therapy with strong steroids and months of therapy with weak steroids. Management. It can be prevented by a judicious use of steroids and a regular monitoring of IOP when steroid therapy is a must.
Treatment consists of:
• Discontinuation of steroids. IOP may normalise within 10 days to 4 weeks in 98% of cases.
• Medical therapy with 0.5% timolol maleate is effective during the normalisation period.
• Filtration surgery is required occasionally in intractable cases.
TRAUMATIC GLAUCOMA
A secondary glaucoma may complicate perforating as well as blunt injuries.
Mechanisms.Traumatic glaucoma may develop by one or more of the following mechanisms:
• Inflammatory glaucoma due to iridocyclitis (see page 249).
• Glaucoma due to intraocular haemorrhage (see page 252).
• Lens-induced glaucoma due to ruptured, swollen or dislocated lens (see page 248).
• Angle-closure due to peripheral anterior synechiae formation following perforating corneal injury producing adherant leucoma.
• Epithelial or fibrous in growth, may involve trabeculum.
• Angle recession (cleavage) glaucoma. Angle recession refers to rupture in the ciliary body face (between scleral spur and iris root). Unilateral open angle glaucoma usually occurs after years (may be 10 years) of blunt trauma. Angle recession is not the cause of glaucoma but just indicator of old trauma. Glaucoma occurs due to slowly-induced fibrosis of trabecular meshwork.
252	Section III   Diseases of Eye


Management includes:
• Medical therapy with topical 0.5% timolol and oral acetazolamide,
• Treatment of associated causative mechanism (e.g., atropine and steroids for control of inflammation), and
• Surgical intervention according to the situation.

CILIARY BLOCK GLAUCOMA
Ciliary block glaucoma (originally termed as malignant glaucoma) is a rare condition which may occur as a complication of any intraocular operation. It classically occurs in patients with primary angle closure glaucoma operated for peripheral iridectomy or filtration (e.g., trabeculectomy) surgery. It is characterised by a markedly raised IOP associated with shallow or absent anterior chamber. Mechanism of rise in IOP. It is believed that, rarely following intraocular operation, the tips of ciliary processes rotate forward and press against the equator of the lens in phakic eyes (cilio-lenticular block) or against the intraocular lens in pseudophakic eyes (cilio-IOL block) or against the anterior hyaloid phase of vitreous in aphakic eyes (cilio-vitreal block) and thus block the forward flow of aqueous humour, which is diverted posteriorly and collects as aqueous pockets in the vitreous (Fig. 10.22). As a consequence of this the iris lens diaphragm is pushed forward, IOP is raised and anterior chamber becomes flat. Clinical features. Patient develops severe pain and blurring of vision following any intraocular operation





















Fig. 10.22 Pockets of aqueous humour in the vitreous in patients with ciliary-block glaucoma

(usually after peripheral iridectomy, filtering surgery or trabeculectomy in patients with primary angle-closure glaucoma). On examination the main features of the ciliary block glaucoma noted are:
• Persistent flat anterior chamber following any intraocular operation,
• Markedly raised IOP in early postoperative period, • Negative Seidel’s test and
• Unresponsiveness or even aggravation by miotics. • Malignant glaucoma may be phakic, aphakic or
pseudophakic.
Management includes:
Medical therapy consists of 1% atropine drops or ointment to dilate ciliary ring and break the cilio-lenticular or cilio-vitreal contact, acetazolamide 250 mg QID and 0.5% timolol maleate eyedrops to decrease aqueous production, and intravenous mannitol to cause deturgescence of the vitreous gel. YAG laser hyaloidotomycan be undertaken in aphakic and pseudophakic patients. If the condition does not respond to medical therapy in 4–5 days.
Surgical therapy in the form of pars plana vitrectomy with or without lensectomy (as the case may be) is required when the above measures fail. It is usually effective, but sometimes the condition tends to recur.
Note. It is important to note that the fellow eye is also prone to meet the same fate.
GLAUCOMAS ASSOCIATED WITH INTRAOCULAR HAEMORRHAGES
Intraocular haemorrhages include hyphaema and/ or vitreous haemorrhage due to multiple causes. These may be associated with following types of glaucomas:
1. Red cell glaucoma. It is associated with fresh traumatic hyphaema. It is caused by blockage of trabeculae by RBCs in patients with massive hyphaema (anterior chamber full of blood). It may be associated with pupil block due to blood clot. Blood staining of the cornea may develop, if the IOP is not lowered within a few days.
2. Haemolytic glaucoma. It is an acute secondary open angle glaucoma due to the obstruction (clogging) of the trabecular meshwork caused by macrophages laden with lysed RBC debris.
3. Ghost cell glaucoma. It is a type of secondary open angle glaucoma which occurs in aphakic or pseudophakic eyes with vitreous haemorrhage. After about 2 weeks of haemorrhage the RBCs degenerate, lose their pliability and become khaki-coloured cells (ghost cells) which pass from the vitreous into the anterior chamber, and block the pores of trabeculae leading to rise in IOP.
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4. Hemosiderotic glaucoma. It is a rare variety of secondary glaucoma occurring due to sclerotic changes in trabecular meshwork caused by the iron from the phagocytosed haemoglobin by the endothelial cells of trabeculum.
GLAUCOMAS ASSOCIATED WITH IRIDOCORNEAL ENDOTHELIAL SYNDROMES
Iridocorneal endothelial (ICE) syndromes include three clinical entities:
• Progressive iris atrophy,
• Chandler’s syndrome, and • Cogan-Reese syndrome.
Pathogenesis. The common feature of the ICE syndromes is the presence of abnormal corneal endothelial cells which proliferate to form an endothelial membrane in the angle of anterior chamber. Glaucoma is caused by secondary synechial angle-closure as a result of contraction of this endothelial membrane.
Clinical features. The ICE syndromes typically affect middle-aged women. The raised IOP is associ-ated with characteristic features of the causative condition.
■In ‘progressive iris atrophy,’ iris features predominate with marked corectopia, atrophy and hole formation. ■While in Chandler’s syndrome, changes in iris are mild to absent and the corneal oedema even at normal IOP predominates.
■Hallmark of Cogan-Reese syndrome is nodular or diffuse pigmented lesions of the iris (therefore also called as iris naevus syndrome) which may or may not be associated with corneal changes.
Treatment is usually frustating:
• Medical treatment is often ineffective, • Trabeculectomy operation usually fails,
• Glaucoma drainage device i.e., artificial filtration shunt may control the IOP.

SURGICAL PROCEDURES FOR GLAUCOMA
PERIPHERAL IRIDECTOMY Indications
1.Treatment of all stages of primary angle-closure glaucoma.
2.Prophylaxis in the fellow eye.
Note. Laser iridotomy should always be preferred over surgical iridectomy.
Surgical technique (Fig. 10.23)
1.Incision. A 4 mm limbal or preferably corneal incision is made with the help of razor blade fragment.









A	B











C	D

Fig. 10.23 Technique of peripheral iridectomy: A, anterior limbal incision to open the anterior chamber; B, prolapse of peripheral iris by pressure at the posterior lip of the incision; C, excision of the prolapsed knuckle of the iris by de Wecker’s scissors; D, suturing the wound

2.Iris prolapsed. The posterior lip of the wound is depressed so that the iris prolapses. If the iris does not prolapse, it is grasped at the periphery with iris forceps.
3.Iridectomy. A small full thickness piece of iris is excised by de Wecker’s scissors.
4.Reposition of iris. Iris is reposited back into the anterior chamber by stroking the lips of the wound or with iris repositors.
5.Wound closure is done with one or two 10–0 nylon sutures with buried knots.
6.Subconjunctival injection of dexamethasone 0.25 ml and gentamicin 0.5 ml is given.
7.Patching of eye is done with a sterile eye pad and sticking plaster.
GONIOTOMY AND TRABECULOTOMY
These operations are indicated in congenital and developmental glaucomas (For details, see page 227)
FILTERING OPERATIONS
Filtering operations provide a new channel for aqueous outflow and successfully control the IOP (below 21 mm of Hg). Filtration  operations can be grouped as below:
A. External filteration surgery
1. Free-filtering operations (Full thickness fistula). These are no longer performed nowadays, because
254	Section III   Diseases of Eye

of high rate of postoperative complications. Their names are mentioned only for historical interest. These operations included Elliot’s sclero-corneal trephining, punch sclerectomy, Scheie’s thermosclerostomy and iridencleisis.
2. Guarded filtering surgery (Partial thickness fistula e.g., trabeculectomy).
3. Non-penetrating filtration surgery e.g., deep sclerectomy and viscocanalostomy.
B. Internal filteration surgery	A	B Note. Salient features of few important filteration
operations are described here.

A. External Filtration Surgery
Trabeculectomy
Trabeculectomy, first described by Carain in 1980 is the most frequently performed partial thickness filtering surgery till date.

Indications
1.Primary angle-closure glaucoma with peripheral anterior synechial involving more than 270° angle or where PI and medical treatment fail.
2.Primary open-angle glaucoma not controlled with medical treatment.
3.Congenital and developmental glaucomas where trabeculotomy and goniotomy fail.
4.Secondary glaucomas where medical therapy is not effective.
Mechanisms of filtration
1.Anew channel (fistula) is created around the margin of scleral flap, through which aqueous flows from anterior chamber into the subconjunctival space.
2.If the tissue is dissected posterior to the scleral spur, a cyclodialysis may be produced leading to increased uveoscleral outflow.
3.When trabeculectomy was introduced, it was thought that aqueous flows through the cut ends of Schlemm’s canal. However, now it is established that this mechanism has a negligible role.
Surgical technique is as below: (Fig. 10.24)
1.Initial steps of anaesthesia, cleansing, draping, exposure of eyeball and fixation with superior rectus suture are similar to cataract operation (see page 201).
2.Conjunctival flap (Fig. 10.24A). A fornix-based or timbal-based conjunctival flap is fashioned and the underlying sclera is exposed. The Tenon’s capsule is cleared away using a Tooke’s knife, and haemostasis is achieved with cautery.
3.Scleral flap (Fig. 10.24B). A partial thickness (usually half) limbal-based scleral flap of 5 mm × 5 mm size is reflected down towards the cornea.




C	D

Fig. 10.24 Technique of trabeculectomy: A, fornix-based conjunctival flap; B & C, partial thickness scleral flap and excision of trabecular tissue; D, peripheral iridectomy and closure of sclera) flap; E, closure of conjunctival) flap

4.Excision of trabecular tissue (Fig. 10.24B): A narrow strip (4 mm × 2 mm) of the exposed deeper sclera near the cornea containing the canal of Schlemm and trabecular meshwork is excised.
5.Peripheral iridectomy (Fig. 10.24C) is performed at 12 O’clock position with de Wecker’s scissors. 6.Closure. The scleral flap is replaced and 10-0 nylon
sutures are applied. Then the conjunctival flap is reposited and sutured with two interrupted sutures (in case of fornix based flap) or continuous suture (in case of limbal-based flap) (Fig. 10.24D).
7.Subconjunctival injections of dexamethasone and gentamicin are given.
8.Patching. Eye is patched with a sterile eye pad and sticking plaster or a bandage.
Complications
A few common complications are postoperative shallow anterior chamber, hyphaema, iritis, cataract due to accidental injury to the lens, and endophthalmitis (not very common).
Use of antimetabolites with trabeculectomy
It is recommended that antimetabolites should be used for wound modulation, when any of the following risk factors for the failure of conventional trabeculectomy are present:
Chapter 10

1.Previous failed filtration surgery. 2.Glaucoma in aphakia.
3.Certain secondary glaucomas e.g., inflammatory glaucoma, post-traumatic angle recession glaucoma, neovascular glaucoma and glaucomas associated with ICE syndrome.
4.Patients treated with topical antiglaucoma medications (particularly sympathomimetics) for over three years.
5.Chronic cicatrizing conjunctival inflammation.
Antimetabolite agents. Either 5-fluorouracil (5-FU) or mitomycin-C can be used. Mitomycin-C is only used at the time of surgery. A sponge soaked in 0.02% (2 mg in 10 ml) solution of mitomycin-C is placed at the site of filtration between the scleral and Tenon’s capsule for 2 minutes, followed by a thorough irrigation with balanced salt solution.

Glaucoma	255








A	B









C	D



Use of collagen implant with glaucoma filtration surgery has been recommended as an alternative to mitomycin–C for modulating wound healing in high risk cases mentioned above. Its effectively is similar to MMC and eliminates the complications associated with MMC. However, collagen matrix implant is more expensive.
Technique. Usually a 6 mm diameter and 1 mm thick implant is sutured over the scleral flap.
Sutureless trabeculectomy 1.Initial steps, and
2.Conjuctival  flap  fashioning  is  similar  to conventional trabeculectomy.
3.Sclero-corneal valvular tunnel, 4 mm × 4 mm in size, is made by first making 4 mm partial thickness scleral groove about 2.5 mm away from the superior limbus with the help of a razor bladefragment (Fig. 10.25A). A 4 mm wide sclero-corneal tunnel which extends about 1.5 mm in the clear cornea is then made with the help of a crescent knife (Fig. 10.25B). 4.Entry into the anterior chamber is made with the
help of a sharp 3.2 mm angled keratome. 5.Punching of posterior lip of the anterior chamber
entry site. (Fig. 10.25C) is then performed with the help of a Kelly’s punch (see Fig. 26.61) to make a sclerostomy of about 2 mm × 2 mm in size.
6.Peripheral iridectomy (Fig. 10.25D) is performed at 12 O’clock position with the help of de Wecker’s or Vanna’s scissors.
7.Closure. Anterior chamber is filled with balanced salt solution (BSS) or air to close the valvular sclero-corneal tunnel incision. Conjunctival flap is reposited and anchored with wet-field cautery.



Fig. 10.25 Sutureless trabeculectomy

Non-penetrating filteration surgeries
Recently some techniques of non-penetrating filteration surgery (in which anterior chamber is not entered) have been advocated to reduce the incidence of postoperative endophthalmitis, overfiltration and hypotony. Main disadvantage of nonpenetrating filteration surgery is inferior IOP control as compared to conventional trabeculectomy. The two currently used procedures are:
1. Deep sclerectomy. In this procedure, after making a partial thickness scleral flap, (as in conventional trabeculectomy, Fig.10.24A), a second deep partial-thickness scleral flap is fashioned and excised leaving behind a thin membrane consisting of very thin sclera, trabeculum and Descemet’s membrane (through which aqueous diffuses out). The superficial scleral flap is loosly approximated and conjunctival incision is closed.
2. Viscocanalostomy. It is similar to deep sclerectomy, except that after excising the deeper scleral flap, high viscosity viscoelastic substance is injected into the Schlemm’s canal with a special cannula.

B. Internal Filteration Surgeries
Internal filteration surgeries, also called as canal-based procedure, are newer techniques that restore filteration through Schlemm’s canal. These are designed to keep the normal anatomy and to be conjunctival bleb free; and thus reducing the risk of long-term endophthalmitis and ocular hypotomy.
256	Section III   Diseases of Eye


These procedure includes:
1. Canaloplasty, i.e., dilatation and circumferential, traction of canal using 10–0 prolene suture.
2. Trabectome  involves an ab interno microcautery that ablates the trabecular meshwork and inner wall of Schlemm’s canal.
3. iStent, is a titanium micro device that is placed inside the Schlemm’s canal. It allows the aqueous humor to flow directly into the canal bypassing the trabecular meshwork.
GLAUCOMA DRAINAGE DEVICE OPERATIONS Glaucoma drainage device or the so called glaucoma valve implants are plastic devices which allow aqueous outflow by creating a communication between the anterior chamber and sub-Tenon’s space. The operation using glaucoma valve implant is also known as Seton operation.
Glaucoma drainage device commonly used include Molteno (Fig. 10.26) Krupin-Denver and  Ahmed glaucoma valve (AGV).
Indications of artificial drainage shunts include: • Neovascular glaucoma,
• Glaucoma with aniridia, and
•  Intractable cases of primary and secondary glaucoma where even trabeculectomy with adjunct antimetabolite therapy fails.
Ex-PRESS glaucoma implant
Ex-PRESS glaucoma implant (mini shunt), is small stainless steel device, which is now implanted under the partial-thickness sclera flap as a modification of




















Fig. 10.26 Artificial drainage shunt operation using Molteno implant

trabeculectomy. It provides a more favorable safety and postoperative recovery profile than standard trabeculectomy. So, it is now alternative to glaucoma drainage valves such as AGV.
CYCLO-DESTRUCTIVE PROCEDURES
Cyclo-destructive procedures lower IOP by destroying part of the secretory ciliary epithelium thereby reducing aqueous secretion.
Indications. These procedures are used mainly in absolute glaucomas.

Cyclo-destructive procedures in current use are:
• Cyclocryotherapy,
• Nd: Yag laser cyclodestruction, and • Diode laser cyclophotocoagulation.
Technique of cyclocryotherapy
1.Anaesthesia. Topical and peribulbar block anaesthesia is given.
2.Lids separation is done with eye speculum. 3.Cryoapplications. Cryo is applied with a retinal
probe placed 3 mm from the limbus. A freezing at – 80°C for 1 minute is done in an area of 180° of the globe (Fig. 10.27).
If ineffective, the procedure may be repeated in the same area after 3 weeks. If still ineffective, then the remaining 180° should be treated.
Mechanism. IOP is lowered due to destruction of the secretory ciliary epithelium. The cells are destroyed by intracellular freezing.




















Fig. 10.27 Site of cyclocryopexy
11

Diseases of Vitreous



Chapter Outline

APPLIED ANATOMY Structure Attachments
DISORDERS OF THE VITREOUS Vitreous liquefaction
•
•
Vitreous detachments Vitreous opacities
•
•
•
•
•
Muscae volitantes
Persistent hyperplastic primary vitreous Inflammatory vitreous opacities
Vitreous aggregates and condensation with liquefaction Amyloid degeneration



APPLIED ANATOMY

Vitreous humour is an inert, transparent, jelly-like structure that fills the posterior four-fifth of the cavity of eyeball. Vitreous body is some what spherical posteriorly and has a cup-shaped depression (patellar fossa) anteriorly. Thus, it conforms to the contour of retina behind and lens infront. It is about 4 ml in volume and 4 gm in weight.
Functions. It is a hydrophilic gel that mainly serves the optical functions. In addition, it mechanically stabilizes the volume of the globe and is a pathway for nutrients to reach the lens and retina. Embryologically, this vitreous body is the secondary or definitive vitreous secreted by neuroectoderm of optic cup. During development, when this secondary vitreous fills the cavity,primary or primitive vitreous (mesenchymal in origin) along with hyaloid vessels is pushed anteriorly and ultimately disappear. Tertiary vitreous is developed from neuroectoderm in the ciliary region and is represented by the ciliary zonules.
Structure
The normal youthful vitreous gel is composed of a network of randomly-oriented collagen fibrils interspersed with numerous spheroidal macromolecules of hyaluronic acid. The collapse

• Asteroid hyalosis Synchysis scintillans
Red cell opacities Tumour cell opacities
•
•
•
Vitreous haemorrhage vitreo-retinal degenerations
VITREcTOMY Techniques
•
•
Open-sky vitrectomy
Closed vitrectomy (Pars plana vitrectomy)
Vitreous substitutes



of this structure with age or otherwise leads to conversion of the gel into sol. The vitreous body can be divided into two parts: the cortex and the medulla or nucleus (the main vitreous body) (Fig. 11.1).
1. Cortical vitreous. It lies adjacent to the retina posteriorly and ciliary body, zonules and lens anteriorly. The density of collagen fibrils is greater in this peripheral part. The condensation of these fibrils form a false anatomic membrane which is called as anterior hyaloid membrane anterior to ora serrata and posterior hyaloid membrane posterior to ora. The attachment of the anterior hyaloid membrane to the posterior lens surface is firm in young and weak in elders, whereas, posterior hyaloid membrane remains loosely attached to the internal limiting membrane of the retina throughout life. These membranes cannot be discerned in a normal eye unless the lens has been extracted and posterior vitreous detachment has occurred.
2. The main vitreous body (medulla or nucleus). It has a less dense fibrillar structure and is a true biological gel. It is here where liquefactions of the vitreous gel start first. Microscopically the vitreous body is homogenous, but exhibits wavy lines as of watered silk in the slit-lamp beams. Running down the centre of the vitreous body from the optic disc to the posterior pole of the lens is the hyaloid canal
258	Section iii   Diseases of Eye























Fig. 11.1 Gross anatomy of the vitreous



(Cloquet’s canal) of doubtful existence in adults. Down this canal ran the hyaloid artery of the foetus.
Attachments
The part of the vitreous about 4 mm across the ora serrata is called as vitreous base, where the attachment of the vitreous is strongest. The other firm attachments are around the margins of the optic disc, foveal region and back of the crystalline lens by hyaloidocapsular ligament of Wiegert.

DISORDERS OF THE VITREOUS

VitreouS LiquefAction
Vitreous liquefaction (synchysis) is the most common degenerative change in the vitreous.
Causes of liquefaction include:
1. Age-related liquefaction is of common occurrence after the age of 50 years.
2. Degenerations such as myopic degeneration , and that associated with retinitis pigmentosa.
3. Post-inflammatory, particularly following uveitis. 4. Trauma to the vitreous which may be mechanical
(blunt as well as perforating).
5. Thermal effects on vitreous following diathermy, photocoagulation and cryocoagulation.
6. Radiation effects may also cause liquefaction. Clinical features. On slit-lamp biomicroscopy the vitreous liquefaction (synchysis) is characterised

by the absence of normal fine fibrillar structure and visible pockets of liquefaction associated with appearance of coarse aggregate material which moves freely in free vitreous. Liquefaction is usually associated with collapse (synersis) and opacities in the vitreous, which may be seen subjectivelyas black floaters in front of the eye.
VitreouS DetAchmentS
1. Posterior vitreous detachment (PVD)
It refers to the separation of the cortical vitreous from the retina anywhere posterior to vitreous base (3–4 mm wide area of attachment of vitreous to the ora serrata).
PVD with vitreous liquefaction (synchysis) and collapse (synersis) is of common occurrence in majority of the normal subjects above the age of 65 years (Fig. 11.2). It occurs in eyes with senile liquefaction, developing a hole in the posterior hyaloid membrane. The synchytic fluid collects between the posterior hyaloid membrane and the internal limiting membrane of the retina, and leads to PVD up to the base along with collapse of the remaining vitreous gel (synersis). These changes occur more frequently in the aphakics than the phakics, and in the myopes than the emmetropes.
Clinical features
■Flashes of light and floaters are often associated with PVD.
Chapter 11	Diseases of Vitreous	259















Fig. 11.2 Posterior vitreous detachment with synchysis and synersis
■Biomicroscopic examination of the vitreous reveals:
• A collapsed vitreous (synersis)behind the lens and an optically clear space between the detached posterior hyaloid phase and the retina.
• A ring-like opacity (Weiss ring or Fuchs ring), representing a ring of attachment of vitreous to the optic disc, is pathognomic of PVD.
Complications of PVD
These include retinal breaks, vitreous haemorrhage, retinal haemorrhages and cystoid maculopathy.
Management
• Uncomplicated PVD requires no treatment. Just reassure but give ‘retinal detachment warning’, i.e., to report immediately on noticing an increase in floaters, or flashing lights or the appearance of persistent curtain or shadow in the field of vision.
• Retinal tear complicating PVD may need to be treated by laser photocoagulation.
• Vitreous haemorrhage complicating PVD needs to be managed (see page 260).
• Retinal detachment complicating PVD requires urgent treatment (see page 300).
2. Detachment of the vitreous base and the anterior vitreous
It may occur following blunt trauma. It may be associated with vitreous haemorrhage, anterior retinal dialysis and dislocation of crystalline lens.
VitreouS oPAcitieS
Since vitreous is a transparent structure, any relatively nontransparent structure present in it will form an opacity and cause symptoms of floaters. Common conditions associated with vitreous opacities are described below.
muscae volitantes
These are physiological opacities and represent the residues of primitive hyaloid vasculature. Patient

perceives them as fine dots and filaments, which often drift in and out of the visual field, against a bright background (e.g., clear blue sky).

Persistent hyperplastic primary vitreous (PhPV)
It results from failure of the primary vitreous structure to regress combined with the hypoplasia of the posterior portion of vascular meshwork. Clinical features. PHPV may be anterior or posterior, most often elements of both are present. Common features are:
■Leucocoria (whitish pupillary reflex) is the most common presenting feature of both anterior and posterior PHPV.
■Microphthalmia is often associated with PHPV. ■Tractional retinal detachment and retinal folds are features of posterior PHPV.
■Associated anomalies include congenital cataract, shallow anterior chamber, angle closure glaucoma, long ciliary processes and recurrent intraocular haemorrhage.
■PHPV is almost always unilateral. Bilateral cases are rare and may be associated with trisomy 13 (Patau syndrome), trisomy 22, Norries disease and Walkers Warburg syndrome.
Differential diagnosis needs to be made from other causes of leucocoria especially retinoblastoma, congenital cataract and retinopathy of prematurity. Computerised tomography (CT) scanning helps in diagnosis by presence of calcification in retinoblastoma.
Treatment consists of pars plana lensectomy and excision of the membranes with anterior vitrectomy provided the diagnosis is made early. Visual prognosis is often poor.

inflammatory vitreous opacities
These consist of exudates poured into the vitreous in patients with anterior uveitis (iridocyclitis), posterior uveitis (choroiditis), pars planitis, pan uveitis and endophthalmitis.

Vitreous aggregates and condensation with liquefaction
It is the commonest cause of vitreous opacities. Condensation of the collagen fibrillar network is a feature of the vitreous degeneration which may be senile, myopic, post-traumatic or post-inflammatory in origin.

Amyloid degeneration
It is a rare condition in which amorphous amyloid material is deposited in the vitreous as a part of the generalised amyloidosis. These vitreous opacities are linear with footplate attachments to the retina and the posterior lens surface.
260	Section iii   Diseases of Eye


Asteroid hyalosis
It is characterised by small, white rounded bodies suspended in the vitreous gel. These are formed due to accumulation of calcium-containing lipids. Asteroid hyalosis is a unilateral, asymptomatic condition usually seen in old patients with healthy vitreous. There is a genetic relationship between this condition, diabetes and hypercholesterolaemia. The genesis is unknown and there is no effective treatment.
Synchysis scintillans (cholestrolosis bulbi)
In this condition, vitreous is laden with small white angular and crystalline bodies formed of cholesterol. It affects the damaged eyes which have suffered from trauma, vitreous haemorrhage or inflammatory disease in the past. In this condition vitreous is liquid and so, the crystals sink to the bottom, but are stirred up with every movement to settle down again with every pause. This phenomenon appears as a beautiful shower of golden rain on ophthalmoscopic examination. Since, the condition occurs in a damaged eye, it may occur at any age. The condition is generally symptomless, and untreatable.
red cell opacities
These are caused by small vitreous haemorrhages or leftouts of the massive vitreous haemorrhage.
tumour cells opacities
These may be seen as free floating opacities in some patients with retino-blastoma, and reticulum cell sarcoma and intraocular lymphomas.
VitreouS hAemorrhAge
Vitreous haemorrhage usually occurs from the retinal vessels and may present as preretinal (sub-hyaloid) or an intragel haemorrhage. The intragel haemorrhage may involve anterior, middle, posterior or the whole vitreous body.
causes
Causes of vitreous haemorrhage are:
1. Retinal tear, PVD and RD may have associated vitreous haemorrhage.
2. Trauma to eye, which may be blunt or perforating (with or without retained intraocular foreign body) in nature.
3. Inflammatory diseases such as erosion of the vessels in acute chorioretinitis and periphlebitis retinae primary (Eales’ disease), or secondary to uveitis.
4. Vascular disorders, e.g., hypertensive retinopathy, and central retinal vein occlusion.
5. Metabolic diseases such as diabetic retinopathy.


6. Exudative age-related macular degeneration usually  high  CNVM,  may  have  vitreous haemorrhage.
7. Blood dyscrasias, e.g., retinopathy of anaemia, leukaemias, polycythemias and sickle-cell retinopathy.
8. Bleeding disorders, e.g., purpura, haemophilia and scurvy.
9. Neoplasms. Vitreous haemorrhage may occur from rupture of vessels due to acute necrosis in tumours like retinoblastoma and malignant melanoma of choroid.
10. Other causes include Coat’s diseases, radiation retinopathy, retinal capillary aneurysm.
clinical features
Depending upon the location it is labeled as: • Anterior vitreous hemorrhage,
• Mid vitreous hemorrhage,
• Posterior vitreous hemorrhage, or • Total vitreous hemorrhage.
Symptoms
• Floaters of sudden onset occur when the vitreous haemorrhage is small.
• Sudden painless loss of vision occurs in massive vitreous haemorrhage.
Signs
• Distant direct ophthalmoscopy reveals black shadowsagainsttheredglowinsmallhaemorrhages and no red glow in a large haemorrhage.
• Direct and indirect ophthalmoscopy may show presence of blood in the vitreous cavity in small vitreous haemorrhage and non-visualization of fundus in large vitreous haemorrhage.
• Slit-lamp examination shows normal anterior segment and a reddish mass in the vitreous.
• Ultrasonography with B-scan is particularly helpful in diagnosing vitreous haemorrhage.
fate of vitreous haemorrhage
1. Complete  absorption  may occur without organization and the vitreous becomes clear within 4–8 weeks.
2. Organization of haemorrhage with formation of a yellowish-white debris occurs in persistent or recurrent bleeding.
3. Complications like vitreous liquefaction, degeneration and khaki cell glaucoma (in aphakia) may occur.
4. Retinitis proliferans may occur which may be complicated by tractional retinal detachment.
Chapter 11	Diseases of Vitreous	261


treatment
1. Conservative treatment consists of bed rest and elevation of patient’s head. This will allow the blood to settle down.
2. Treatment of the cause. Once the blood settles down, indirect ophthalmoscopy should be performed to locate and further manage the causative lesion such as a retinal break, phlebitis, proliferative retinopathy, etc.
3. Vitrectomy by pars plana route should be considered to clear the vitreous, if the haemorrhage is not absorbed after 3 months. Early vitrectomy may be required when associated with retinal detachment.
Vitreo-retinAL DegenerAtionS See page 290.

VITRECTOMY

Vitrectomy, i.e., surgical removal of the vitreous is now a frequently performed procedure. Common terms used in relation to vitrectomy are:
• Anterior vitrectomy. It refers to removal of anterior part of the vitreous.
• Core vitrectomy. It refers to removal of the central bulk of the vitreous. It is usually indicated in endophthalmitis.
• Subtotal and total vitrectomy. In this almost whole of the vitreous is removed.
techniqueS open-sky vitrectomy
This technique is employed to perform only anterior vitrectomy.
Indications
• Vitreous loss during cataract extraction. • Aphakic keratoplasty.
• Anterior chamber reconstruction after perforating trauma with vitreous loss.
• Removal of subluxated and anteriorly dislocated lens.
Surgical technique
Open-sky vitrectomy is performed through the primary wound to manage the disturbed vitreous during cataract surgery or aphakic keratoplasty. It should be performed using an automated vitrectomy machine. However, if the vitrectomy machine is not available, it can be performed with the help of a triangular cellulose sponge and de Wecker’s scissors (sponge vitrectomy).
closed vitrectomy (pars plana vitrectomy)
Pars plana approach is employed to perform anterior vitrectomy, core vitrectomy, subtotal and total vitrectomy.


Indications
• Endophthalmitis with vitreous abscess. • Vitreous haemorrhage.
• Proliferative retinopathies such as those associated with diabetes, Eales’ disease, retinopathy of prematurity and retinitis proliferans.
• Complicated cases of retinal detachment such as those associated with giant retinal tears, retinal dialysis and massive vitreous traction. Presently, even simple cases of rhegmatogenous retinal detachment are managed with this technique.
• Removal of intraocular foreign bodies.
• Removal of dropped nucleus or intraocular lens from the vitreous cavity.
• Persistent primary hyperplastic vitreous. • Vitreous membranes and bands.
• Macular pathology like macular hole, and epiretinal membrane.
Surgical techniques
Pars plana vitrectomy is a highly sophisticated microsurgery which can be performed by using two type of systems:
1.One-port vitrectomy or full function system vitrectomy is nowadays not used. It employs a multifunction system that comprises vitreous infusion, suction, cutter and illumination (VISC), all in one.
2. Three-port pars plana vitrectomy or divided system approach isthemostcommonlyemployedtechnique in modern vitrectomy. In this technique three separate incisions are given in pars plana region. That is why the procedure is also called three-port 20 gauze pars plana vitrectomy. The cutting and aspiration functions are contained in one probe, illumination is provided by a separate fiberoptic probe and infusion is provided by a cannula introduced through the third pars plana incision (Fig. 11.3).
Advantagesof divided system approachinclude smaller instruments, easy handling, improved visualization, use of bimanual technique and adequate infusionby separate cannula.
23 and 25 gauge three-port vitrectomy techniques introduced recently are becoming increasingly popular alternatives to the standard 20 gauge vitrectomy. Their advantages include self-sealing sclerotomy sites, improved patient comfort, reduced postoperative inflammation and more rapid visual recovery.

VitreouS SubStituteS
Vitreous substitutes or the so called tamponading agents are used in vitreoretinal surgery to:
262	Section iii   Diseases of Eye























Fig. 11.3 Three-port pars plana vitrectomy using divided system approach

• Restore intraocular pressure, and • Provide intraocular tamponade.

An ideal vitreous substitute should be:
• Having a high surface tension, • Optically clear, and
• Biologically inert.

Currently used vitreous substitutes in the absence of an ideal substitute are:
1. Air is commonly used internal tamponade in uncomplicated cases. It is absorbed within 3 days. 2. Physiological solutions such as Ringer’s lactate or balanced salt solution (BSS) can be used as substitute after vitrectomy for endophthalmitis or uncomplicated vitreous haemorrhage.
3. Expanding gases are preferred over air in complex cases requiring prolonged intraocular tamponade. They are used as 40% mixture with air. Examples are:
• Sulphur hexafluoride (SF6). It doubles its volume and lasts for 10 days.
• Perfluoropropane (C3 F8). It quadruples its volume and lasts for 28 days.
4. Perfluorocarbon liquids (PFCLs) are heavy liquids which are mainly used:
• To remove dropped nucleus or IOL from the vitreous cavity,
• To unfold a giant retinal tear, and
• To stabilize the posterior retina during peeling of the epiretinal membrane.
Agents  used  are  perfluoro-n-octane,  per-fluoro-tributylamine, perfluorodecalin and perfluorophenanthrene.
5. Silicone oil allows more controlled retinal manipulation during operation and can be used for prolonged intraocular tamponade after retinal detachment surgery.
12

Diseases of Retina



CHAPTER OUTLINE

APPLIED ANATOMY
CONGENITAL AND DEVELOPMENTAL DISORDERS OF RETINA
INFLAMMATORY DISORDERS OF RETINA Retinitis
•
•
Retinal vasculitis
VASCULAR DISORDERS OF RETINA Retinal artery occlusions
•
•
•
•
•
•
•
•
Retinal vein occlusions Hypertensive retinopathy
Retinopathy in pregnancy induced hypertension Diabetic retinopathy
Sickle-cell retinopathy Retinopathy of prematurity Retinopathies of blood disorders



APPLIED ANATOMY

Retina, the innermost tunic of the eyeball, is a thin, delicate and transparent membrane. It is the most highly-developed tissue of the eye. It appears purplish-red due to the visual purple of the rods and underlying vascular choroid.
Gross Anatomy
Retina extends from the optic disc to the ora serrata with a surface area of about 266 mm2. Retina is thickest in the peripapillary region (0.56 mm) and thinnest at ora serrate (0.1 mm). Grossly, it can be divided into two distinct regions: posterior pole and peripheral retina separated by the so called retinal equator.
■Retinal equator is an imaginary line which is considered to lie in line with the exit of the four vena verticose.
Posterior pole refers to the area of retina posterior to the retinal equator. The posterior pole of the retina includes two distinct areas: the optic disc and macula lutea (Fig. 12.1). Posterior pole of the retina is best examined by slit-lamp indirect biomicroscopy using +78 D and +90 D lens and by direct ophthalmoscopy.

• Primary retinal telangiectasia Ocular ischaemic syndrome
DYSTROPHIES AND DEGENERATIONS OF RETINA Retinal dystrophies
•
•
•
Retinal degenerations MACULAR DISORDERS
RETINAL DETACHMENT
• Rhegmetogenous Exudative Tractional
•
•
TUMOURS OF RETINA
• Retinoblastoma Enucleation Phacomatoses
•
•


Optic disc. It is a pink coloured, well-defined vertically oval area with average dimension of 1.76 mm horizontally and 1.88 mm vertically. It is placed 3.4 mm nasal to the fovea. At the optic disc all the retinal layers terminate except the nerve fibres (1–1.2 million), which pass through the lamina cribrosa to run into the optic nerve. The optic disc thus represents the beginning of the optic nerve and so is also referred to as optic nerve head. A depression seen in the disc is called the physiological cup. The central retinal artery and vein emerge through the centre of this cup. Because of absence of photoreceptors (rods and cones), the optic disc produces an absolute scotoma in the visual field called as physiological blind spot.
Macula lutea. It is also called the yellow spot. It is comparatively deeper red than the surrounding fundus and is situated at the posterior pole temporal to the optic disc. It is about 5.5 mm in diameter. Fovea centralis is the central depressed part of the macula. It is about 1.5 mm in diameter and is the most sensitive part of the retina. With lowest threshold for light and highest visual acuity, because it contains only cones, in its centre is a shining pit called foveola (0.35 mm diameter) which is situated about 2 disc diameters
264	Section 3   Diseases of Eye















A















B


















C
Fig. 12.1 Gross anatomy of the retina: A, parts of retina in horizontal section at the level of fovea; B, diagrammatic fundus view; C, fundus photograph

(3–4 mm) away from the temporal margin of the disc and about 1 mm below the horizontal meridian. The tiny depression in the centre of foveola is called umbo which is seen as shinning foveal reflex on fundus examination. An area about 0.8 mm in diameter (including foveola and some surrounding area) does not contain any retinal capillaries and is called foveal avascular zone (FAZ). Surrounding the fovea are the parafoveal and perifoveal areas.
Peripheral retina refers to the area bounded posteriorly by the retinal equator and anteriorly by the ora serrata. Peripheral retina is best examined with indirect ophthalmoscopy and by the use of Goldman three mirror contact lens.
Ora serrata.It is the serrated peripheral margin where the retina ends. Here the retina is firmly attached both to the vitreous and the choroid. The pars plana extends anteriorly from the ora serrata.
Microscopic structure
Retina consists of ten layers, arranged in two distinct functional components the pigment epithelium and the neurosensory retina with a potential space between the two. The neurosensory retina consists of three types of cells and their synapses (Fig. 12.2): 1. Pigment epithelium. It is the outermost layer of retina. It consists of a single layer of cells containing pigment. It is firmly adherent to the underlying basal lamina (Bruch’s membrane) of the choroid. Pigment epithelium provides metabolic support to the neurosensory retina and also acts as an antireflective layer. Interphotoreceptor matrix (IPM) is present in the potential space between pigment epithelium and the neurosensory retina and constitutes a strong binding mechanism between the two (by binding pigment epithelium to the photoreceptor). ■Constituent molecules of IPM include: Inter-photoreceptor retinal binding protein (IRBP), proteoglycan-glycosaminoglycans (sulphated and nonsulphated chondroitin and hyaluronic acid), fibronectin, sialoprotein associated with rods and cones (SPARC), intercellular adhesion molecules, hyaluronic acid receptor (CD44 antigen), and lysosomal enzymes (matrix metalloproteinases and tissue inhibitors of metalloproteinases, i.e., TIMP). 2. Layer of rods and cones. Rods and cones are the end organs of vision and are also known as photoreceptors. Layer of rods and cones contains only the outer segments of photoreceptor cells arranged in a palisade manner. There are about 120 millions rods and 6.5 millions cones. Rods contain a
Chapter 12	Diseases of Retina	265


























Fig. 12.2 Microscopic structure of the retina


photosensitive substance visual purple (rhodopsin) and subserve the peripheral vision and vision of low illumination (scotopic vision). Cones also contain a photosensitive substance and are primarily responsible for highly discriminatory central vision (photopic vision) and colour vision.
3. External limiting membrane. It is a fenestrated membrane, through which pass processes of the rods and cones.
4. Outer nuclear layer. It consists of nuclei of rods and cones.
5. Outer plexiform layer. It consists of connections of rod spherules and cone pedicles with the dendrites of bipolar cells and horizontal cells.
6. Inner nuclear layer. It mainly consists of cell bodies of bipolar cells. It also contains cell bodies of horizontal, amacrine and Muller’s cells and capillaries of central artery of retina. The bipolar cells constitute the first order neurons.
7. Inner plexiform layer. It essentially consists of connections between the axons of bipolar cells and dendrites of the ganglion cells, and processes of amacrine cells.
8. Ganglion cell layer. It mainly contains the cell

bodies of ganglion cells (the second order neurons of visual pathway). There are two types of ganglion cells. The midget ganglion cells are present in the macular region and the dendrite of each such cell synapses with the axon of single bipolar cell. Polysynaptic ganglion cells lie predominantly in peripheral retina and each such cell may synapse with up to a hundred bipolar cells.
9. Nerve fibre layer (stratum opticum) consists of axons of the ganglion cells, which pass through the lamina cribrosa to form the optic nerve. For distribution and arrangement of retinal nerve fibres see Figures 10.12 and 10.13, respectively and page 233.
10. Internal limiting membrane. It is the innermost layer and separates the retina from vitreous. It is formed by the union of terminal expansions of the Muller’s fibres, and is essentially a basement membrane.
Structure of fovea centralis
In this area (Fig. 12.3), there are no rods, cones are tightly packed and other layers of retina are very thin. Its central part (foveola) largely consists of cones and their nuclei covered by a thin internal limiting
266	Section 3   Diseases of Eye

























Fig. 12.3 Microscopic structure of the fovea centralis

membrane. All other retinal layers are absent in this region. In the foveal region surrounding the foveola, the cone axons are arranged obliquely (Henle’s layer) to reach the margin of the fovea.
Functional divisions of retina
Functionally, retina can be divided into temporal retina and nasal retina by a line drawn vertically through the centre of fovea. Nerve fibres arising from temporal retina pass through the optic nerve and optic tract of the same side to terminate in the ipsilateral geniculate body while the nerve fibres originating from the nasal retina after passing through the optic nerve cross in the optic chiasma and travel through the contralateral optic tract to terminate in the contralateral geniculate body. Neurons of geniculate body constitutes the third order neurons in visual pathway.
Blood supply
Outer four layers of the retina, viz, pigment epithelium, layer of rods and cones, external limiting membrane and outer nuclear layer are avascular get their nutrition from the choroidal and vascular system formed by contribution from anterior ciliary arteries and posterior ciliary arteries.
Inner six layers of retina are vascular and get their supply from the central retinal artery, which is a

branch of the ophthalmic artery. In some individuals cilioretinal artery (branch from posterior ciliary arteries) is present as a congenital variation and supplies the macular area. In such cases central vision is retained in the eventuality of central retinal artery occlusion (CRAO).
Central retinal artery emerges from centre of the physiological cup of the optic disc and divides into four branches, namely the superior-nasal, superior-temporal, inferior-nasal and inferior-temporal. These are end arteries, i.e., they do not anastomose with each other. However, anastomosis between the retinal vessels and ciliary system of vessels (short posterior ciliary arteries) does exist with the vessels which enter the optic nerve head from the arterial circle of Zinn or Haller. Branches of this circle invade lamina cribriosa and also send branches to the optic nerve head (optic disc) and the surrounding retina. The retinal veins. These follow the pattern of the retinal arteries. The central retinal vein drains into the cavernous sinus directly or through the superior ophthalmic vein. The only place where the retinal system anastomosis with ciliary system is in the region of lamina cribrosa.
Blood supply of optic nerve head (see page 311).

CONGENITAL AND DEVELOPMENTAL DISORDERS OF RETINA

Classification
1. Anomalies of the optic disc. These include crescents, sites inverses, congenital pigmentation, coloboma, drusen and hypoplasia of the optic disc.
2. Anomalies of the nerve fibres, e.g., medullated (opaque) nerve fibres.
3. Anomalies of vascular elements, such as persistent hyaloid artery and congenital tortuosity of retinal vessels.
4. Anomalies of the retina proper. These include albinism, congenital night blindness, congenital day blindness, Oguchi’s disease, congenital retinal cyst, congenital retinal detachment and coloboma of the fundus.
5. Congenital anomalies of the macula are aplasia, hypoplasia and coloboma.
A few important congenital disorders are described briefly.

COLOBOMA OF THE OPTIC DISC
It results from the failure in closure of the embryonic fissure. It occurs in two forms.
Chapter 12	Diseases of Retina	267



Minor defect is more common and manifests as inferior crescent, usually in association with hypermetropic or astigmatic refractive error.
Fully-developed coloboma typically presents inferonasally as a very large whitish excavation, which apparently looks as the optic disc. The actual optic disc is seen as a linear horizontal pinkish band confined to a small superior wedge. Defective vision and  superior visual field defect is usually associated.
DRUSEN OF THE OPTIC DISC
Drusens are intrapapillary refractile bodies, which usually lie deep beneath the surface of the disc tissue in childhood and emerge out by the early teens. Thus, in children they present as pseudo-papilloedema and by teens they can be recognised ophthalmoscopically as waxy pea-like irregular retractile bodies.
HYPOPLASIA OF OPTIC DISC
Hypoplasia of the optic nerve may occur as an isolated anomaly or in association with other anomalies of central nervous system. The condition is bilateral in 60% of cases. It is associated with maternal alcohol use, diabetes and intake of certain drugs in pregnancy. It forms a significant cause of blindness at birth in developed countries. Diagnosis of mild cases presents little difficulty. In typical cases the disc is small and surrounded by a yellowish and a pigmented ring; referred to as ‘double ring sign’.
MEDULLATED NERVE FIBRES
These, also known as opaque nerve fibres, represent myelination of nerve fibres of the retina. Normally, the medullation of optic nerve proceeds from brain downwards to the eyeball and stops at the level of lamina cribrosa. Occasionally, the process of myelination continues after birth for an invariable distance in the nerve fibre layer of retina beyond the optic disc. On ophthalmoscopic examination, these appear as a whitish patch with feathery margins, usually present adjoining the disc margin. The traversing retinal vessels are partially concealed by the opaque nerve fibres (Fig. 12.4). Such a lesion, characteristically, exhibits enlargement of blind spot on visual field charting. The medullary sheaths disappear in demyelinating disorders and optic atrophy (due to any cause) and thus no trace of this abnormality is left behind.
PERSISTENT HYALOID ARTERY
Congenital remnants of the hyaloid arterial system may persist in different forms.














Fig. 12.4 Opaque nerve fibres

Bergmester’s papilla refers to the flake of glial tissue projecting from the optic disc. It is the commonest congenital anomaly of the hyaloid system. Vascular loop or a thread of obliterated vessel may sometimes be seen running forward into the vitreous. It may even be reaching up to the back of the lens.
Mittendorf dot represents remnant of the anterior end of hyaloid artery, attached to the posterior lens capsule. It is usually associated with a posterior polar cataract.

INFLAMMATORY DISORDERS OF RETINA
These may present as retinitis (pure retinal inflammation), chorioretinitis (inflammation of retina and choroid), neuroretinitis (inflammation of optic disc and surrounding retina), or retinal vasculitis (inflammation of the retinal vessels).
RETINITIS
I. Nonspecific retinitis
It is caused by pyogenic organisms and may be either acute or subacute.
1. Acute purulent retinitis. It occurs as metastatic infection in patients with pyaemia. The infection usually involves the surrounding structures and soon converts into metastatic endophthalmitis or even panophthalmitis.
2. Subacute retinitis of Roth. It typically occurs in patients suffering from subacute bacterial endocarditis (SABE). It is characterised by multiple superficial retinal haemorrhages, involving posterior part of the fundus. Most of the haemorrhages have a white spot in the centre (Roth’s spots). Vision may be
268	Section 3   Diseases of Eye



blurred due to involvement of the macular region or due to associated papillitis.
II. Specific retinitis
It may be bacterial (tuberculosis, leprosy, syphilis and actinomycosis), viral (cytomegalic inclusion disease, rubella, herpes zoster), mycotic, rickettsial or parasitic in origin.
Cytomegalovirus (CMV) retinitis (Fig. 12.5), zoster retinitis, progressive outer retinal necrosis (PORN) caused by an aggressive variant of varicella zoster virus, and acute retinal necrosis (ARN) caused by herpes simplex virus II (in patients under the age of 15 years) and by varicella zoster virus and herpes simplex virus-I (in older individuals) have become more conspicuous in patients with AIDS (HIV infection).
RETINAL VASCULITIS
Inflammation of the retinal vessels wall may be primary (Eales’ disease) or secondary to uveitis.
Eales’ disease
It is an idiopathic inflammation of the peripheral retinal veins. It is characterised by recurrent vitreous haemorrhage; so also referred to as primary vitreous haemorrhage. The disease is rare in Caucasians but is an important cause of visual morbidity in young Asian males.
Etiology. It is not known exactly. Many workers consider it to be a hypersensitivity reaction to tubercular proteins.
Clinical features. It is a bilateral disease, typically affecting young adult males (20–30 years). The common presenting symptoms are:















Fig. 12.5 Fundus photograph showing typical cytomeg­ alovirus (CMV) retinitis in a patient with AIDS. Note white necrotic retinal associated with retina haemorrhages

•  Sudden appearance of floaters (blackspots) in front of the eye or
•  Sudden painless loss of vision due to vitreous haemorrhage. The haemorrhage clears up but recurrences are very common.
Clinical course of the Eales’ disease can be described in four stages:
1. Stage of active inflammation (active retinal vasculitis) (Fig. 12.6). The affected peripheral veins are congested and perivascular exudates and sheathing are seen along their surface. Superficial haemorrhages ranging from flame-shaped to sheets of haemorrhages may be present near the affected veins.
2. Stage of ischaemia or vascular occlusion is characterized by obliteration of the involved vessels and development of areas of capillary non-perfusion (CNP) in the periphery as evidenced on fundus fluorescein angiography.
3. Stage of retinal neovascularization is marked by development of abnormal fragile vessels at the junction of perfused and non-perfused retina. Bleeding from these vessels leads to recurrent vitreous haemorrhage.
4. Stage of sequelae or advance stage of disease is characterized by development of complications such as proliferative vitreoretinopathy, fractional retinal detachment, rubeosis iridis and neovascular glaucoma.
Treatment of Eales’ disease comprises:
1. Medical treatment. Course of oral corticosteroids for extended periods is the mainstay of treatment















Fig. 12.6  Fundus photograph of a patient with Eales’ disease (stage of inflammation). Note venous congestion, perivascular exudates and sheets of haemorrhages present near the affected veins
Chapter 12	Diseases of Retina	269



during stage of active inflammation. A course of antitubercular therapy has also been recommended in selective cases.
2. Laser photocoagulation of the retina either PRP or feeder vessel photocoagulation is indicated in stage of neovascularizion.
3. Vitreoretinal surgery is required for non-resolving vitreous haemorrhage and fractional retinal detachment.

VASCULAR DISORDERS OF RETINA

Common vascular disorders of retina include: retinal artery occlusions, retinal vein occlusions, diabetic retinopathy, hypertensive retinopathy, sickle cell retinopathy, retinopathy of prematurity and retinal telangiectasia.
RETINAL ARTERY OCCLUSIONS
Etiology
Occlusive disorders of retinal vessels are more common in patients suffering from hypertension and other cardiovascular diseases. Common causes of retinal artery occlusion are:
1. Emboli from the carotid artery and those of cardiac origin are the most common cause of CRAO. Three types of emboli are known:
• Cholesterol emboli (Hollenhorst plaque) are refractile and orange and seen at retinal vessel bifurcation. These arise from atheromas in the carotid artery.
• Calcium emboli are white in colour and arise from the cardiac valves.
• Platelet fibrin emboli are dull white in colour and arise from atheromas in the carotid artery. They may cause retinal ischaemic attacks (TIA).
2. Atherosclerosis-related thrombosis at the level of lamina cribrosa is another common cause of CRAO. 3. Retinal arteritis with obliteration (associated with giant cell arteritis) and periarteritis (associated with polyarteritis nodosa, systemic lupus erythematosus, Wegner’s granulomatosis and scleroderma) are other causes of CRAO.
4. Angiospasm is a rare cause of retinal artery occlusion. It is commonly associated with amaurosis. 5. Raised intraocular pressure may occasionally be associated with obstruction of retinal arteries, for example, due to tight encirclage in retinal detachment surgery.
6. Thrombophilic disorders such as inherited defects of anticoagulants may occasionally be associated with CRAO in young individuals.

7. Other rare causes are retinal migraine, sickling haemoglobinopathies and hypercoagulation disorders such as oral contraceptives, polycythemia, and antiphospholipid syndrome.
Clinical features
Clinically retinal artery occlusion may present as central retinal artery occlusion (60%) or branch artery occlusion (35%) or cilioretinal artery occlusion (5%). It is more common in males than females. It is usually unilateral but rarely may be bilateral (1 to 2% cases).
1. Central retinal artery occlusion (CRAO)
It occurs due to obstruction at the level of lamina cribrosa.
Symptoms.Patient complains of sudden painless loss of vision occurring over seconds. Patient may give history of transient visual loss (amaurosis fugax) in the past. Signs of CRAO are as below:
1. Visual acuity is markedly reduced (<3/60 in 90% cases) except in a few cases with cilioretinal artery supplying the macula (Fig. 12.7).
2. Direct pupillary reflex is absent and relative afferent pupillary defect (RAPD) is positive.
3. Fundus examination shows (Fig. 12.7):
• Marked narrowing of retinal arteries and mild narrowing of retinal veins.
• Retina becomes milky white due to ischaemic oedema. In eyes with cilioretinal artery part of macula remains normal in colour (Fig. 12.7A).
• Cherry-red spot is seen in the center of macula due to vascular choroid shining through the thin retina in foveal region, in contrast to the surrounding pale retina (Fig. 12.7B).
• Cattle tracking, i.e., segmentation of blood column is seen in the retinal veins.
• Atrophic changes. In most cases retinal oedema resolves over a period of 4–6 weeks and atrophic changes in the form of grossly attenuated thread like arteries atrophic appearing retina and consecutive optic atrophy occur in long standing cases (see Fig. 12.12B)
4. Fundus fluorescein angiography(FFA) shows delay in arterial filing (cilioretinal artery when present will fill in early phase) and masking of choroidal vasculature due to retinal oedema.
2. Branch retinal artery occlusion (BRAO)
It usually occurs following lodgement of embolus at a bifurcation. Retina distal to occlusion becomes oedematous with narrowed arterioles (Fig. 12.8). Later on the involved area is atrophied leading to permanent sectoral visual field defect.
270	Section 3   Diseases of Eye

















A












B
Fig. 12.7 Fundus photograph showing marked retinal pallor in acute central retinal artery occlusion (CRAO): A, with sparing of the territory supplied by cilioretinal artery; and B, cherry­red spot in the absence of cilioretinal artery
Management
Treatment of central retinal artery occlusion is unsatisfactory, as retinal tissue cannot survive ischaemia for more than 90–100 minutes.
A. Aggressive treatment of acute episodes of CRAO should be done in all cases presenting within 24 hours of onset with following measures:
1. Immediate lowering of intraocular pressure may aid the arterial perfusion and also help in dislodging the embolus, measure include:
• Intermittent ocular massage, intravenous mannitol, • Paracentesis of anterior chamber has been
recommended for this purpose, and
• Intravenous acetazolamide 500mg should be given immediately.
2. Vasodilators and inhalation of a mixture of 5% carbon dioxide and 95% oxygen (practically patient should be asked to breathe in a polythene bag) may help by relieving element of angiospasm.

Fig. 12.8 Superotemporal branch of retinal artery occlusion (BRAO). Note retinal pallor in superotemporal area and whitish emboli on the optic disc and in superior temporal branch of retinal artery

3. Fibrinolytic therapy may be helpful in some cases. 4. Intravenous steroids are indicated in patients with giant cell arteritis.
5. Laser photodisruption of the embolus has been reported in selected cases to dislodge the embolus.
B. Work-up for associated systemic conditions should be carried out immediately after the emergency management of acute episodes and corrective measures instituted.
Complications
In some cases ‘neovascular glaucoma’ with incidence varying from 2% to 6%, may occur as a delayed complication of central retinal artery occlusion.
RETINAL VEIN OCCLUSIONS
Retinal vein occlusions are more common than the artery occlusions. These typically affect elderly patients in sixth or seventh decade of life.
Etiology
1. Pressure on the vein by an atherosclerotic retinal artery where the two share a common adventitia (e.g., just behind the lamina cribrosa and at arteriovenous crossings), secondarily induces thrombosis in the lumen of vein.
2. Hypertension and diabetes mellitus are common predisposing factors.
3. Hyperviscosity of blood as in polycythemia, hyperlipidemia, macroglobulinemia, leukemia, multiple myeloma, cryoglobulinemia.
4. Periphlebitis retinae which can be central or peripheral associated with sarcoidosis, syphillis, and SLE.
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5. Raised intraocular pressure. Central retinal vein occlusion is more common in patients with primary open-angle glaucoma.
6. Local causes are orbital cellulitis, orbital tumors, facial erysipelas and cavernous sinus thrombosis.
Classification
1. Central retinal vein occlusion (CRVO). It may be non-ischaemic CRVO (venous stasis retinopathy) or ischaemic CRVO (haemorrhagic retinopathy).
2. Branch retinal vein occlusion (BRVO).

Centeral Retinal Vein Occlusion
Non-ischaemic CRVO
Non-ischaemic CRVO (venous stasis retinopathy) is the most common clinical variety (75%). It is characterised by mild to moderate visual loss and no RAPD.
Early cases on fundus examination (Fig. 12.9) reveal mild venous congestion and tortuosity, a few superficial flame-shaped haemorrhages more in the peripheral than the posterior retina, mild papilloedema and mild or no macular oedema.
In late stages (after 6–9 months), there appears sheathing around the main veins, and a few cilioretinal collaterals around the disc. Retinal haemorrhages are partly absorbed. Macula may show chronic cystoid oedema in moderate cases or may be normal in mild cases.
Note. About 15% cases of non-ischaemic CRVO are converted to ischaemic CRVO in 4 months and about 30% in 3 years.
Ischaemic CRVO
Ischaemic CRVO (haemorrhagic retinopathy) refers to acute (sudden) complete occlusion of central retinal vein. It is characterised by marked sudden visual loss and RAPD.














Fig. 12.9 Central retinal vein occlusion (non­ischaemic)

Early cases on fundus examination (Fig. 12.10) reveal:
• Massive engorgement, congestion and tortuousity of retinal veins,
• Massive retinal haemorrhages (almost whole fundus is full of haemorrhages giving a ‘splashed-tomato’ appearance),
• Numerous cotton wool spots (usually more than 6 to 10),
• Disc shows oedema and hyperaemia,
• Macular area is full of haemorrhages and is severely oedematous and
• Break through vitreous haemorrhage may be seen in some cases.
In late stages, marked sheathing around veins and collaterals is seen around the disc.
• Neovascularization may be seen at the disc (NVD) or in the periphery (NVE).
• Macula shows marked pigmentary changes and chronic cystoid oedema.
Pathognomonic features for ischaemic CRVO differentiating it from non-ischaemic CRVO are:
• Presence of relative afferent pupillary defect (RAPD),
• Visual field defects, and
• Reduced amplitude of b-wave of electroretinogram. Complications. Rubeosis iridis and neovascular glaucoma (NVG) occurs in about 20% cases within 3 months (so also called as 90 days glaucoma), a few cases develop vitreous haemorrhage and proliferative retinopathy.
Branch retinal vein occlusion (BRVO)
It is more common than the central retinal vein occlusion. It may occur as:
• Hemispheric occlusion due to occlusion in themain branch at the disc.














Fig. 12.10 Central retinal vein occlusion (ischaemic)
272	Section 3   Diseases of Eye



• Quadrantic occlusion due to occlusion at the level of AV crossing, and
• Small branch occlusion either as macular branch occlusion or peripheral branch occlusion.

Features of BRVO are as below:
■Retinal oedema and haemorrhages are limited to the area drained by the affected vein (Fig. 12.11). Vision is affected only when the macular area is involved.
■Secondary glaucoma occurs rarely in these cases. ■Chronic macular oedema and neovascularization may occur as complications of BRVO in about one third cases.

Management of retinal vein occlusions A. Clinical evaluation and investigations
I. Ocular examination and investigations
Ocular examination should include:
• Visual acuity, at presentation and at every follow up, is a useful guide for the interventions required.
• IOP should be recorded and associated POAG should be ruled out.
• Undilated slit-lamp examination to detect neovascularization of iris (NVI).
• Gonioscopy to rule out neovascularization of angle (NVA).
• Fundus examination with direct and indirect ophthalmoscopy  and  with  90D  slit-lamp examination.

Ocular investigations should include:
• Goldmann perimetry and ERG evaluation is very important in differentiating between ischaemic and non-ischaemic CRVO.














Fig. 12.11 Superotemporal branch of retinal vein occlusion (BRVO)

• Fundus fluorescein angiography (FFA) should be carried out (to assess state of retinal perfusion) after resolution of retinal haemorrhage. Usually areas of capillary non-perfusion (CNP) of more than 10 disc area are seen in ischaemic CRVO.
• Optical coherence tomography (OCT) is particularly useful for evaluation of macular oedema, sub-retinal fluid accumulation and development of epiretinal membrane (ERM).
II. Systemic examination and investigations
Systemic associations which need to be looked for are: • Hypertension, diabetes mellitus, heart diseases,
dyslipidaemia,
• Hypercoagulative conditions, and
• Homocysteinosis, especially in young patients.

B. Differential diagnosis
Diabetic retinopathy is generally bilateral and CRVO is usually unilateral.
Ocular ischaemic syndrome (OIS) due to carotid occlusive disease has only dilated veins without tortuosity (in CRVO tortuosity is also seen) and retinal haemorrhages are typically seen in the mid periphery.
C. Treatment
I. Treatment of systemic and ocular associations such as hypertension, diabetes, hyperlipidaemias, hyperhomocysteinaemia, POAG, and other conditions is important in all cases. Smoking should be avoided.
II. Observation and monitoring is all that is required in patients with mild to moderate visual loss (VA better than 6/18), as the condition (especially non-ischaemic CRVO), in more than 50% cases of CRVO resolves with almost normal vision.
III.Ocular therapy, as described below, is required in patients presenting with marked visual loss (usually ischaemic CRVO) and those with progressive visual loss on observation.
1. Medical therapy, presently in vogue is: ■Intravitreal anti-VEGFs, e.g., 1.25 mg Bevacizumab (Avastin), or 0.3 mg Ranibizumab (Lucentis) are useful for the associated CME and neovascularization. ■Intravitreal triamcinolone (1 mg/0.1 ml) may be given for the associated CME.
Note. Repeated injections of anti-VEGFs, and triamcinolone may be required.
2. Laser therapy, recommended is as below:
■Grid laser is NOT recommended for macular oedema in CRVO. However, persistent CME in BRVO may be treated by grid laser.
Chapter 12	Diseases of Retina	273



■Panretinal photocoagulation (PRP) is generally not recommended as prophylaxis even in cases with marked ischaemia (except in patients not likely to comply with regular follow-up). PRP should be performed without delay in CRVO when neovascularization develops any where, i.e., in angle (NVA), iris (NVE), retina (NVE & NVD). PRP involves application of 1500–3000 burns (0.5–1.0 second), spaced one burn width apart using frequency doubling YAG laser or argon green laser. ■Scatter laser photocoagulation is recommended for neovascularization else where (NVE) in patients with BRVOs.
3. Surgical therapy may be required in the form of
1. Pars plana vitrectomy for treating the following complications associated with venous occlusions: • Persistent vitreous haemorrhage,
• Tractional retinal detachment,
• Epiretinal membrane (ERM), and
• Intractable neovascular glaucoma (NVG).
Note. PPV may be combined with endolaser PRP when required.
i. Pars plana placement of glaucoma drainage device (GDD) may also be required in patients with NVG. ii. Radical optic neurotomy, once proposed by transvitreal incision of the scleral ring (along with PPV) to surgically decompress CRV at the level of scleral outlet, has not proved useful.

HYPERTENSIVE RETINOPATHY
Hypertensive retinopathy refers to fundus changes occurring in patients suffering from systemic hypertension. Although the term hypertensive retinopathy implies only retinal changes but in fact the clinical presentation includes changes of hypertensive:
• Retinopathy,
• Choroidopathy, and • Optic neuropathy.

Pathogenesis
Three factors which play role in the pathogenesis of hypertensive retinopathy are vasoconstriction, arteriosclerosis and increased vascular permeability. 1. Vasoconstriction. Arteriolar narrowing is the primary response to raised blood pressure and is related to the severity of hypertension.
• Vasoconstriction of retinal arterioles occurs in pure form in young individuals, but is affected by the pre-existing involutional sclerosis in older patients.

• Vasoconstriction of choroidal vessels causes choroidal and RPE ischaemia, which manifests as hypertensive choroidopathy.
• Vasoconstriction of peripapillary choroid leads to optic nerve head ischaemia, manifesting as hypertensive optic neuropathy.
2. Arteriosclerotic changeswhich manifest as changes in the arteriolar reflex and A-V nipping result from thickening of the vessel wall and are a reflection of the duration of hypertension. In older patients arteriosclerotic changes may pre-exist due to involutional sclerosis.
3. Increased vascular permeability results fromhypoxia and is responsible for haemorrhages, exudates, focal retinal oedema, macular oedema, focal intraretinal periarterial transudates (FIPTs), and disc oedema.
Clinical types
Clinically, the hypertensive fundus changes can be described as:
• Chronic hypertensive retinopathy, and
• Malignant or acute hypertensive retinopathy.
Chronic hypertensive retinopathy
Patients with chronic hypertensive retinopathy are usually asymptomatic. Clinical situations in which chronic hypertensive retinopathy occurs include:
1. Hypertension with involutionary (senile) sclerosis When hypertension occurs in elderly patients (after the age of 50 years) in the presence of involutionary sclerosis the fundus changes comprise augmented arteriosclerotic retinopathy.
2. Chronic hypertension with compensatory arteriolar sclerosis
This condition is seen in young patients with prolonged benign hypertension usually associated with benign nephrosclerosis. The young arterioles respond by proliferative and fibrous changes in the media (compensatory arteriolar sclerosis). Advanced fundus changes in these patients have been described as ‘albuminuric or renal retinopathy.’
Fundus changes of chronic hypertensive retinopathy can be summarized as below (Fig. 12.12A to C):
1. Generalized arterial narrowing or attenuation, depending upon the severity of hypertension may be mild or marked, and consists of vasoconstrictive and sclerotic phases.
• Vasoconstrictive phase occurs due to diffuse vasospasm which manifests when a significant elevation of blood pressure has persisted for an appreciable period and is characterised by an increase in retinal arteriolar tone.
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• Sclerotic phase occurs due to intimal thickening, hypoplasia of tunica media, and hyaline degeneration; and is characterised by arteriolar narrowing associated with tortuosity.
2. Focal arteriolar narrowing is seen as areas of localized vasoconstriction on the disc and within ½ disc diameter of its margin zone.
3. Arteriovenous nickingis the hallmark of hypertensive retinopathy and occurs where arteriole crosses and compresses the vein, as the vessels share a common adventitious sheath. Also known as A-V crossing changes, these include:
• Salu’s sign, i.e., deflection of veins at the arteriovenous crossings,
• Bonnet sign, i.e., banking of veins distal to arteriovenous crossings, and
• Gunn sign, i.e., tapering of veins on either side of the crossings.
4. Arteriolar reflex changes. The normal light reflex of the retinal vasculature is formed by the reflection from the interface between the blood column and vessel wall.
• Bright and thin, linear blood reflex is seen normally over the surface of the arteriole in the young age and is predominantly because of blood column in the arteriole, since the vessel wall is by and large transparent.
• More diffuse and less bright reflex is seen due to thickening of vessel wall and represents changes of grade I and II hypertensive retinopathy.
• Copper wiring, i.e., reddish-brown reflex of the arterioles occurs due to progressive sclerosis and hyalinization, and is a sign of grade III retinopathy.
• Silver wiring i.e., opaque–white reflex of the arterioles occurs ultimately due to the continued sclerosis, and is seen in grade IV hypertensive retinopathy.
5. Superficial retinal haemorrhages (flame shaped) occur at the posterior pole due to disruption of the capillaries in the retinal nerve fibre layer. These haemorrhages disappear in 3 to 5 weeks.
6. Hard exudates are lipid deposits in the outer plexiform layer of retina which occur following leaky capillaries in severe hypertensive retinopathy. They appear as yellowish waxy spots with sharp margins. They are generally seen in posterior pole and may be arranged as macular-fan or macular-star. They are also temporary and may disappear in 3–6 weeks. 7. Cotton wool spots are fluffy white lesions and represent the areas of infarcts in the nerve fibre layer. These occur due to ischaemia caused by

capillary obliterations in severe hypertensive retinopathy. Due to their cotton wool feathery appearance they are also termed as soft exudates (a misnomer in fact).
Malignant hypertensive retinopathy
Malignant hypertension is not a separate variety of hypertension, but is an expression of its rapid progression to a serious degree in a patient with relatively young arterioles undefended by fibrosis.
Fundus picture is characterised by changes of acute hypertensive retinopathy, choroidopathy and optic neuropathy (Fig. 12.12D):
I. Acute hypertensive retinopathy changes include:
• Marked arteriolar narrowing due to spasm of the arteriolar wall, in response to sudden rise in blood pressure.
• Superficial retinal haemorrhages, flame shaped, arranged in clusters, appear in the posterior pole area due to disruption of capillaries in the nerve fibre layer.
• Focal intraretinal periarteriolar transudates (FIPTs) are small, white, focal oval lesions occurring due to the deposition of macromolecules along the major arterioles. These result due to break down of blood-retinal barrier following dilatation of terminal arterioles as a result of sudden rise in blood pressure in malignant hypertension.
• Cotton wool spots are also more marked in malignant hypertensive retinopathy.
• Microaneurysms, shunt vessels and collaterals may also develop as a result of capillary obliterations.
II.Acute hypertensive choroidopathy changes include: • Acute focal retinal pigment epitheliopathy, characterised by focal white spots, occurs due to
acute ischaemic changes in choriocapillaries.
• Elschnig’s spots are small black spots surrounded by yellow halos, these are formed due to clumping and atrophy of the infarcted pigment epithelium (focal white spots) described above.
• Siegrist  streaks  are formed due to linear configuration of the pigment along the choroidal arterioles. These are formed due to fibrinoid necrosis associated with malignant hypertension.
• Serous neurosensory retinal detachment, which preferentially affects the macular area, may occur due to accumulation of fluid beneath the retina following breakdown of outer blood-retinal barrier owing to ischemic damage to the retinal pigment epithelium. It may also manifest as exudative bullous retinal detachment with shifting subretinal fluid.
Chapter 12	Diseases of Retina	275














A	B












C	D
Fig. 12.12 Hypertensive retinopathy: A, grade I; B, grade II; C, grade III; D, grade IV



III. Acute hypertensive optic neuropathy changes include:
• Disc oedema and hemorrhages on the disc and peripapillary retina which occur due to vasoconstriction of peripapillary choroidal vessels supplying the optic nerve head. The ischemia of the optic nerve head leads to stasis of axoplasmic flow, thus the lesion is a form of anterior ischaemic optic neuropathy.
• Disc pallor, of variable degree, may occur late in the course of disease.

Staging of Hypertensive Retinopathy
Several classification schemes have been described to stage hypertensive retinopathy. No classification is clinically useful. A few popular classifications, are given below, just for their historical value.
Keith and Wagner classification
• Grade I. Mild generalized arteriolar attenuation, particularly of small branches, with broadening of the arteriolar light reflex and vein concealment (Fig. 12.12A).


• Grade II. Marked generalized narrowing and focal attenuation of arterioles associated with deflection of veins at arteriovenous crossings (Salus’ sign) (Fig. 12.12B).
• Grade III. Grade II changes plus copper-wiring of arterioles, banking of veins distal to arteriovenous crossings (Bonnet sign), tapering of veins on either side of the crossings (Gunn sign) and right-angle deflection of veins (Salu’s sign). Flame-shaped haemorrhages, cotton-wool spots and hard exudates are also present (Fig. 12.12C).
• Grade IV. All changes of grade III plus silver-wiring of arterioles and papilloedema (Fig. 12.12D).
Scheie classification
Staging of retinopathy changes is as follows:
• Stage 0. No visible retinal abnormalities
• Stage 1. Diffuse arteriolar narrowing; no focal constriction
• Stage 2. More pronounced arteriolar narrowing with focal constriction
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• Stage 3. Focal and diffuse narrowing, with retinal haemorrhages
• Stage 4. Retinal oedema, hard exudates, optic disc edema

Grading of the light reflex changes resulting from arteriolosclerosis is as follows:
• Grade 0. Normal
• Grade 1. Broadening of light reflex with minimal arteriolovenous compression
• Grade 2. Light reflex changes and arteriovenous crossing changes more prominent
• Grade 3. Copper-wire appearance and more prominent arteriolovenous compression
• Grade 4. Silver-wire appearance and severe arteriolovenous crossing changes.
Wong and McIntosh classification
Mild retinopathy is characterised by one or more of the following signs: generalised arteriolar narrowing, focal arteriolar narrowing, AV nicking, arteriolar wall reflex broadening. There is weak associations with stroke, coronary heart disease and cardiovascular mortality.
Moderate retinopathy consists of mild retinopathy with one or more of the following signs: retinal haemorrhages (blot and dot or flame shaped) microaneurysms, cotton-wool spots, and hard exudates. There is strong association with stroke, congestive heart failure, renal dysfunction and cardiovascular mortality.
Accelerated retinopathy consists of moderate retinopathy signs plus optic disc swelling, may be associated with visual loss. Associated with mortality and renal failure.

Management
Mild hypertensive retinopathy requires blood pressure control only.
Moderate  hypertensive  retinopathy  patients (characterised  by  retinal  haemorrhages, microaneurysms, and cotton-wool spots) in addition to blood pressure control benefit from further assessment of vascular risk factors (e.g., cholesterol levels) and, if indicated, risk reduction therapy (e.g., cholesterol lowering agents).
Accelerated hypertensive retinopathy characterized by bilateral disk swelling which may occur in conjunction with severe hypertension needing urgent antihypertensive management. In such instances, physicians should aim for a small stepwise control of blood pressure over a few hours, and avoid a sudden

reduction in blood pressure which may reduce perfusion of optic nerve head and central nervous system (causing stroke).
Note. With adequate hypertension treatment, resolution of signs may occur over a period of up to a year. Thus follow-up of patients for a year may be needed.

Retinopathy in Pregnancy-induced Hypertension
Pregnancy-induced hypertension (PIH), previously known as ‘toxaemia of pregnancy’, is a disease of unknown etiology characterised by raised blood pressure, proteinuria and generalised oedema. Retinal changes are liable to occur in this condition when blood pressure rises above 160/100 mm of Hg and are marked when blood pressure rises above 200/130 mm of Hg.
• Earliest changes consist of narrowing of nasal arterioles, followed by generalised narrowing.
• Severe persistent spasm of vessels causes retinal hypoxia characterised by appearance of ‘cotton wool spots’ and superficial haemorrhages.
• Further progression of retinopathy occurs rapidly if pregnancy is allowed to continue.
• Retinal oedema and exudation is usually marked and may be associated with ‘macular star’ or ‘flat macular detachment.’ Rarely, it may be complicated by bilateral exudative retinal detachment.
• Prognosis for retinal reattachment is good, as it occurs spontaneously within a few days of termination of pregnancy.
Management. Changes of retinopathy are reversible and disappear after the delivery, unless organic vascular disease is established.
• In preorganic stage when patient responds well to conservative treatment, the pregnancy may justifiably be continued under close observation.
• Advent of hypoxic retinopathy (cotton wool spots, retinal oedema and haemorrhages), however, should be considered an indication for termination of pregnancy; otherwise, permanent visual loss or even loss of life (of both mother and foetus) may occur.
DIABETIC RETINOPATHY
Diabetic retinopathy (DR) refers to retinal changes seen in patients with diabetes mellitus. With increase in the life expectancy of diabetics, the incidence of diabetic retinopathy (DR) has increased. Diabetic retinopathy is a leading cause of blindness.
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Etiopathogenesis
Risk factors
1. Duration of diabetes is the most important determining factor.
• After 10 years, 20% of type I and 25% of type II diabetics develop retinopathy.
• After 20 years, 90% of type I and 60% of type II diabetics develop retinopathy.
• After 30 years, 95% of both type I and type II diabetics develop retinopathy.
Note. It is important to note that it is the duration of disease after the onset of puberty which acts as a risk factor. For example, the risk of retinopathy is roughly same for two 30 years old patients, of whom one developed DM at 12 years and other at the age of 4 years, because both have same duration of disease (18 years) after the onset of puberty (i.e. after the age of 12 years).
2. Age of onset of diabetes also act as a risk factor. The risk of retinopathy in a child with onset of diabetes at the age of 2 years is negligible for the first 10 years. After onset of puberty, age of onset is not a risk factor. 3. Sex. Incidence is more in females than males (4:3). 4. Poor metabolic control is less important than duration, but is nevertheless relevant to the development and progression of DR.
5. Heredity. It is transmitted as a recessive trait without sex linkage. The effect of heredity is more on the proliferative retinopathy.
6. Pregnancy may accelerate the changes of diabetic retinopathy.
7. Hypertension, when associated, may also accentuate the changes of diabetic retinopathy.
8. Other risk factors include smoking, obesity, anaemia and hyperlipidaemia.
Pathogenesis
Hypergylcemia, in uncontrolled diabetes mellitus, is the starting point for development of DR. Microangiopathy, affecting retinal pre-capillary arterioles, capillaries and venules, produced by hyperglycaemia is the basic pathology in diabetic retinopathy.
Mechanisms by which hyperglycemia produces microangiopathy include:
i. Cellular damage. Hyperglycaemia produces damage to the cells of retina, endothelial cells, loss of pericytes and thickning of basement membrane of capillaries by following effects:
• Sorbitol accumulation in the cells due to aldose reductase mediated glycolysis,


• Advanced glycation end (AGE) product accumulates in the cells due to non-enzymatic binding of several sugars to proteins,
• Activation of several protein kinase C isoforms, and • Excessive oxidative stress to the cells due to excess
of free radicals.
ii. Hematological and biochemical changes induced by hyperglycaemia which play role in the development of microangiopathy include:
• Platelet adhesiveness increase, • Blood viscosity increase,
• Red blood cells deformation and Rouleaux formation,
• Serum lipids altered abnormally,
• Leukostasis increase due to increased intracameral adhesion molecule-1-(ICAM-1) level expression, and
• Fibrinolysis increase.
Effects of microangiopathy producing DR include:
• Breakdown of blood-retinal barrier leads to retinal oedema, haemorrhages, and leakage of lipids (hard exudates).
• Weakened capillary wall produces micro-aneurysms, and haemorrhages.
• Microvascular occlusions produce ischaemia and its effects, and arteriovenous shunts, i.e., intra-retinal microvascular abnormalities (IRMAs).
Neovascularization of retina is induced by:
• Proangiogenic factors such as vasculoendothelial growth factors (VEGFs), platelet derived growth factor (PDGF), and hepatocyte growth factor (HGF) which are released as a result of ischaemia produced by microvascular occlusions. Release of angiogenic factors is also mediated by hyperglycemia-induced oxidative stress, activation of protein kinase C and cytokines.
• Deletion of anti–angiogenic factors such as en-dostatin, angiostatin, pigment epithelial derived factor (PEDF), thrombospondin-1 and platelet fac-tor 4, also play role in causing neovascularization. Speculated pathogenesis of DR based on the above described changes is summarized in a flowchart
(Fig 12.13).

Classification of Diabetic Retinopathy Diabetic retinopathy has been variously classified. Presently followed classification is as follows:
I. Non-proliferative diabetic retinopathy (NPDR) • Mild NPDR
• Moderate NPDR • Severe NPDR
• Very severe NPDR
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Fig. 12.13 Flowchart depicting pathogenesis of diabetic retinopathy