II. Proliferative diabetic retinopathy (PDR) III. Diabetic maculopathy
IV. Advanced diabetic eye disease (ADED)

I. Non-proliferative diabetic retinopathy (NPDR) Ophthalmoscopic features of NPDR include:
• Microaneurysms are seen in the macular area (the earliest detectable lesion) and elsewhere in relation to area of capillary nonperfusion. These are formed due to focal dilation (out pouching) of capillary wall following loss of pericytes. These appear as red dots and leak fluid, proteins, lipids and also fluorescein dye on FFA.
• Retinal haemorrhages. Both deep (dot and blot haemorrhages which are more common) and superficial haemorrhages (flame-shaped), occur from capillary leakage.
• Retinal oedema characterized by retinal thickening is caused by capillary leakage.
• Hard exudates—yellowish-white waxy-looking patches are arranged in clumps or in circinate pattern. These are commonly seen in the macular area. These occur due to chronic localised oedema and are composed of leaked lipoproteins and lipid filled macrophages.
• Cotton-wool spots, are small whitish fluffy superficial lesions. These represent areas of nerve fibre infarcts.

• Venous abnormalities (beading, looping and dilatation) occur adjacent to area of capillary non-perfusion.
• Intraretinal microvascular abnormalities (IRMA) seen as fine irregular red lines connecting arterioles with venules, represent arteriovenular shunts.
• Dark-blot haemorrhages representing haemor-rhagic retinal infarcts.
ETDRS study classification: On the basis of severity of the above findings the NPDR has been further clas-sified as under:
1. Mild NPDR (Fig. 12.14A).
• At least one microaneurysm must be present. 2. Moderate NPDR (Fig. 12.14B)
• Microaneurysms/intraretinal haemorrhage in 2 or 3 quadrants.
• Early mild IRMA.
• Hard/soft exudates may or may not present.
3. Severe NPDR. Any one of the following (4–2–1 Rule) (Fig. 12.14C):
• Four quadrants of microaneurysms and extensive intraretinal haemorrhages.
• Two quadrants of venous beading. • One quadrant of IRMA changes.
4. Very severe NPDR. Any two of the following (4–2–1 Rule) (Fig. 12.14D):
• Four quadrants of microaneurysms and extensive intraretinal haemorrhages.
• Two quadrants of venous beading. • One quadrant of IRMA changes.
Risk factors for progression to PDR,observed in ETDRS include presence of:
• IRMAs,
• Multiple increasing intraretinal haemorrhages, • Venous beading and loops, and
• Wide spread capillary non-perfusion (CNP) areas.
Note. Interestingly cotton wool spots were not found to be significant predictors.
II. Proliferative diabetic retinopathy (PDR) Proliferative diabetic retinopathy (Figs. 12.14E and F) develops in more than 50% of cases after about 25 years of the onset of disease. Therefore, it is more common in patients with juvenile onset diabetes. ■Occurrence of neovascularization over the changes of very severe non-proliferative diabetic retinopathy is hallmark of PDR. It is characterised by proliferation of new vessels from the capillaries, in the form of neovascularization at the optic disc (NVD) and/or elsewhere (NVE) in the fundus, usually along the course of the major temporal retinal vessels. These
Chapter 12	Diseases of Retina	279












A	B









C	D










E	F	G
Fig. 12.14 Diabetic retinopathy: A, mild NPDR; B, moderate NPDR; C, severe NPDR; D, very severe NPDR; E, early PDR; F, high­risk PDR; G, focal exudative diabetic maculopathy


new vessels may proliferate in the plane of retina or spread into the vitreous as vascular fronds. Later on results in formation of:
• Fibrovascular epiretinal membrane formed due to condensation of connective tissue around the new vessels.
• Vitreous detachment and vitreous haemorrhage may occur in this stage.
Types.On the basis of high-risk characteristics (HRCs) described by diabetic retinopathy study (DRS) group, the PDR can be further classified as below:
1. Early NVD or NVE PDR without HRCs (Early PDR) (Fig. 12.14E), and
2. PDR with HRCs. High-risk characteristics (HRC) of PDR are as follows (Fig. 12.14F):

• NVD 1/4 to 1/3 of disc area with or without vitreous haemorrhage (VH) or preretinal haemorrhage (PRH)
• NVD <1/4 disc area with VH or PRH • NVE >1/2 disc area with VH or PRH
III. Diabetic maculopathy
Changes in macular region need special mention, due to their effect on vision. These changes may be associated with non-proliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR). The diabetic macular oedema (DME) occurs due to increased permeability of the retinal capillaries.
Clinically significant macular oedema (CSME)
CSME is the term coined during early treatment diabetic retinopathy study (ETDRS). It is diagnosed
280	Section 3   Diseases of Eye



if one of the following three criteria are present on slit-lamp examination with 90D lens:
• Thickening of the retina at or within 500 micron of the centre of the fovea.
• Hard exudates at or within 500 micron of the centre of fovea associated with adjacent retinal thickening.
• Development of a zone of retinal thickening one disc diameter or larger in size, at least a part of which is within one disc diameter of the foveal centre.
Clinico-angiographic classification of diabetic maculopathy
1. Focal exudative maculopathy (Fig. 12.14G). It is characterised by microaneurysms, haemorrhages, well-circumscribed macular oedema and hard exudates which are usually arranged in a circinate pattern. Fluorescein angiography reveals focal leakage with adequate macular perfusion.
2. Diffuse exudative maculopathy. It is characterised by diffuse retinal oedema and thickening throughout the posterior pole, with relatively few hard exudates. Fluorescein angiography reveals diffuse leakage at the posterior pole.
3. Ischaemic maculopathy. It occurs due to microvascular blockage. Clinically, it is characterised by marked visual loss with microaneurysms, haemorrhages, mild or no macular oedema and a few hard exudates. Fluorescein angiography shows areas of non-perfusion which in early cases are in the form of enlargement of foveal avascular zone (FAZ), later on areas of capillary dropouts are seen and in advanced cases precapillary arterioles are blocked.
4. Mixed maculopathy. In it combined features of ischaemic and exudative maculopathy are present.
OCT classification of diabetic macular oedema.
On the basis of OCT examination the diabetic macular oedema (DME) has been classified as below: 1. Non-tractional DME. It may be of following types: a. Spongy thickness of macula (>250 µ),
b. Cystoid macular oedema (CME), and
c. Neurosensory detachment with or without (a) or (b) above.
2. Tractional DME. It may be of following types: a. Vitreo-foveal traction (VFT), and
b. Taut/thickened posterior hyaloid membrane.
Note. The OCT classification has a bearing on the management since non-tractional DME is treated conservatively whereas tractional DME is purely treated by pars-plana vitrectomy (PPV) with removal of posterior hyaloid.

IV. Advanced diabetic eye disease
It is the end result of uncontrolled proliferative diabetic retinopathy. It is marked by complications such as:
• Persistent vitreous haemorrhage,
• Tractional retinal detachment, and • Neovascular glaucoma.

Management
Management of diabetic retinopathy includes its screening investigation and treatment.
A. Screening for diabetic retinopathy
To prevent visual loss occurring from diabetic retinopathy a periodic follow-up is very important for a timely intervention. The recommendations for periodic fundus examination are as follows:
• First examination, 5 years after diagnosis of type 1 DM and at the time of diagnosis in type 2 DM.
• Every year, till there is no diabetic retinopathy or there is mild NPDR.
• Every 6 months, in moderate NPDR. • Every 3 months, in severe NPDR.
• Every 2 months, in PDR with no high-risk chara-cteristics.
B. Investigations in a case of DR include: • Urine examination
• Blood sugar estimation • 24 hour urinary protein • Renal function tests
• Lipid profile • Haemogram
• Glycosylated haemoglobin (HbA1C)
• Fundus fluorescein angiography should be carried out to elucidate areas of neovascularization, leakage and capillary nonperfusion.
• Optical  coherence  tomography  (OCT)  to study detailed structural changes in diabetic maculopathy.
C. Treatment of diabetic retinopathy
Treatment modalities for diabetic retinopathy include metabolic control of DM and associated risk factors, intravitreal anti-VEGF drugs, intravitreal steroids, laser therapy, and pars plana vitrectomy. I. Metabolic control of diabetes mellitus and associated risk factors. It is of first and foremost importance to stabilize DM metabolically. Not only the blood glucose levels be in the normal range but other biochemical parameters should also be normal. In case these are deranged consultation from an internist/endocrinologist should be sought. The normal values as under should be targeted:
Chapter 12	Diseases of Retina	281



• Control of glycaemia. Target blood glucose level: fasting <120 mg%, post-prandial <180 mg%, and HbA1c (glycosylated haemoglobin) <7%.
• Control of dyslipidaemia. Target lipid profile (fasting): Cholesterol <200 mg%, Triglycerides <150 mg%, HDL >50 mg%, and LDL <150 mg%.
• Renal function tests. Target level are serum creatinine 1.0 mg%, blood urea 20–40 mg%, and 24-hour urinary protein <200 mg%.
• Control of associated anaemia. Target hemoglobin >10 mg%.
• Control of associated hypertension. Target blood pressure levels:130/80 mm Hg.
• Life style changes. Patients should be counselled toprohibit smoking and alcohol consumption, and take regular exercises.
II. Intravitreal anti-VEGF drugs. Vascular endothelial growth factor (VEGF) plays a pivotal role in the etiopathogenesis of diabetic maculopathy and retinopathy. Anti-VEGFs, e.g., Bevacizumab (1.25 mg) and Ranibizumab (0.5 mg) when given intravitrealy in 0.1 ml vehicle lead to improvement in vision in >40% cases and stabilize vision in another >40% cases. These drugs should be preferred over laser therapy particularly in patients with:
• Focal CME involving centre of fovea, • Diffuse DME,
• Diabetic CME, and
• DME with neurosensory detachment
• Anti-VEGFs are also recommended before pan-retinal photocoagulation (PRP) in patients with PDR and diffuse DME.
Note. Effects of the anti-VEGFs last for 4–6 weeks and frequent injections are warranted. In addition the cost factor and risk of endophthalmitis are the deterrent of anti-VEGF therapy.
III. Intravitreal steroids. Intravitreal triamcinolone acetonide (IVTA) (20 mg) is another drug which is being tried. It restores inner retinal barrier and has some anti-VEGF effects as well. However, risk of glaucoma, steroid induced cataract, and increased vulnerability to endophthalmitis restrict its use. Hence, anti-VEGFs are preferred over IVTA these days. However, in recalcitrant cases IVTA may be given along with anti-VEGFs.
IV. Laser therapy. ETDRS had recommended focal laser for focal DME and grid laser for diffuse DME. Laser helps possibly by stimulating the RPE pump mechanism and by inhibiting VEGF release. Till recently laser therapy, which only stabilizes the vision, was the mainstay in the treatment of DME.

However, with the introduction of anti-VEGF drugs, which also improve vision, the role of laser therapy has become limited. Laser therapy is performed using double frequency YAG laser 532 nm or argon green laser, or diode laser. Protocols for laser therapy as far now are as below:
i. Macular photocoagulation. It is of two types:
• Focal photocoagulation (Fig. 12.15A). It is the treatment of choice for focal DME not involving the centre of fovea.
• Grid photocoagulation (Fig. 12.15B). It is no more the treatment of choice for diffuse DME. It may be considered only for recalcitrant cases not responding to anti-VEGFs and intravitreal steroids. Note. Macular photocoagulation is contraindicated
in ischemic maculopathy and tractional DME.
ii. Panretinal photocoagulation (PRP) or scatter laser consists of 1200–1600 spots, each 500 mm in size and 0.1 sec duration. Laser burns are applied outside the temporal arcades and on nasal side one disc diameter from the disc upto the equator. The burns should be one burn width apart (Fig. 12.15C).
In PRP inferior quadrant of retina is first coagulated. PRP produces destruction of hypoxic retina which is responsible for the production of vasoformative factors.

Indications for PRP are:
■PDR with HRCs, ■Neovascularization of iris (NVI), ■Severe NPDR associated with:
• Poor compliance for follow-up,
• Before cataract surgery/YAG capsulotomy, • Renal failure,
■One eyed patient, and ■Pregnancy.
Note. A shot of anti-VEGF drug intravitrealy given before PRP may protect the macula as well as reduce the risk of vitreous haemorrhage. Further, intravitreal triamcinolone may be considered as an adjunct to PRP.
V. Surgical treatment is indicated in following cases: • Tractional DME with NPDR. Treatment of choice
is pars plana vitrectomy (PPV) with removal of posterior hyaloid.
• Advanced PDR with dense vitreous haemorrhage. PPV along with removal of opaque vitreous gel and endophotocoagulation should be done at an early stage.
• Advanced PDR with extensive fibrovascular epiretinal membrane should be treated by PPV
282	Section 3   Diseases of Eye











A	B	C
Fig. 12.15 Protocols of laser application in diabetic retinopathy: A, focal treatment; B, grid treatment and; C, panretinal photocoagulation



along with removal of fibrovascular epiretinal membrane and endophotocoagulation.
• Advanced PDR with tractional retinal detachment should be treated by PPV with endopho-tocoagulation and reattachment of detached retina along with other methods like scleral buckling and internal tamponade using intravitreal silicone
oil or gases like sulphur hexafluoride (SF6) or
perfluoropropane (C3F8).
RETINOPATHIES OF BLOOD DISORDERS These are seen in patients suffering from sickel cell anaemias, leukaemias and polycythemias.

Sickle-cell Retinopathy
Retinal changes in patients suffering from sickle cell haemoglobinopathies (abnormal haemoglobins) are primarily caused by retinal hypoxia; which results from blockage of small blood vessels by the abnormal-shaped rigid red blood cells.
Clinical features
Sickle-cell retinopathy can be divided into five self-explanatory stages as follows:
1. Stage of peripheral arteriolar occlusion and ischaemia.
2. Stage of peripheral arteriovenous anastomoses. 3. Stage of neovascularization.
4. Stage of vitreous haemorrhage.
5. Stage of vitreoretinal traction bands and tractional retinal detachment.
Treatment
• Panretinal photocoagulation (PRP) is effective in regressing the neovascularization.
• Pars plana vitrectomy is required for vitreoretinal tractional bands. It should be followed by repair of the retinal detachment, when present.

Anaemic Retinopathy
In anaemia, retinal changes are liable to occur when haemoglobin level falls by 50% and are consistently present when it is below 35% (5 gm%). Duration and type of anaemia do not influence the occurrence of retinopathy.
Pathogenesis involves factors like anoxia, venous stasis, angiospasm, increased capillary permeability, and thrombocytopenia.
Characteristc features of anaemic retinopathy are as below:
• Fundus background becomes pale • Retinal arterioles are also pale
• Retinal veins are tortuous and dilated
• Retinal haemorrhages, superficial flame shaped and preretinal (subhyaloid) may be seen in the posterior half of fundus
• Roth spots, i.e., haemorrhages with white center and platelet-fibrin emboli constitute the white centre
• Cotton wool spots may also be seen especially in patients with coexisting thrombocytopenia in aplastic anaemia.

Management includes:
• Treatment of anemia, which leads to reversal of retinopathy in most cases.
• Intervention for a large subhyaloid haemorrhage, which does not resolve spontaneously, in the form of intravitreal tissue plasminogen activator (tPA), or YAG posterior hyaloidotomy, or pars plana vitrectomy, may be required.

Leukaemic Retinopathy
Ocular involvement is more common with acute than chronic leukaemia.
Chapter 12	Diseases of Retina	283



Characteristic features of leukaemic retinopathy include:
• Fundus background is pale and orangish • Retinal veins are tortuous and dilated
• Retinal arterioles become pale and narrow
• Perivascular leukaemic infiltrates, seen as grayish white lines along the course of veins, are seen in latter stages
• Roth spots, i.e., retinal haemorrhages with typical white centre are very common
• Subhyaloid haemorrhage i.e., large preretinal haemorrhages may also be seen.

Other ocular changes in leukaemia include:
• Orbital infiltration, particularly in children presenting as proptosis
• Ocular haemorrhages in the form of subconj-unctival haemorrhage and hyphaema (bleeding in anterior chamber)
• Iris changes in the form of iris thickening and iritis • Pseudohypopyon, i.e., collection of white cells in
the anterior chamber.

RETINOPATHY OF PREMATURITY
Retinopathy of prematurity (ROP) is a bilateral proliferative retinopathy, occurring in premature infants with low birth weight who often have been exposed to high concentration of oxygen. Earlier this disease was known as retrolental fibroplasia.
Etiopathogenesis
Primary risk factors include:
• Low gestation age, especially <32 weeks
• Low birth weight (<1500 g, especially <1250 g), • Supplemental oxygen therapy, and
Other risk factors reported include light, vitamin E deficiency, respiratory distress syndrome, asphyxia, shock, and acidosis.
Pathogenesis In the normal development of retina, the vessels reach the nasal periphery after 8 months of gestation and temporal periphery about 1 month after delivery, by the effect of VEGF.
In premature birth, the production of VEGF is downregulated and vessel migration is halted. However, with growing age, because of increased metabolic demands, the oxygen regulated vasculo-endothelial growth factors (VEGFs) and non-oxygen regulated insulin like growth factors (IGF-1) are produced in excess resulting in neovascularization and fibrous proliferation progressively resulting in different stages of retinopathy of prematurity described below.

Clinical features
The condition has been divided into active ROP and cicatricial ROP. International classification of ROP (ICROP) is based on the stage, zone and extent of ROP.
Staging of ROP
Clinically, the evolution of ROP has been divided into five stages (Fig. 12.16):
• Stage 1. Demarcation line formation at the edge of vessels, dividing the vascular from the avascular retina.
• Stage 2. The line structure of stage 1 acquires a volume to form a ridge with height and width.
• Stage 3. Ridge with extraretinal fibrovascular proliferation into the vitreous. This stage is further subdivided into mild, moderate and severe, depending on the amount of fibrovascular proliferation.
• Stage 4a. Subtotal retinal detachment not involving the macula is a feature of this stage. It occurs as a result of exudation from incompetent blood vessels or traction from the fibrous (cicatricial) tissue.
• Stage 4b. Subtotal retinal detachment involving the macula occur in this stage.
• Stage 5. Total retinal detachment which is always funnel-shaped.
Zones of ROP
The retina is divided into three zones. The centre of the retinal map for ROP is the optic disc not the macula as in other retinal charts (Fig. 12.17).
Diseases of the retina
Zone I
A circle drawn on the posterior pole, with the optic disc as the centre and twice the distance from the centre of disc to fovea as the radius, constitutes zone I. Any ROP in this zone is usually very severe because of a large peripheral area of avascular retina.
Zone II
A circle is drawn with the optic disc as the centre and the distance from the centre of disc to nasal ora serrata as the radius. The area between zone I and this boundary constitutes zone II.
Zone III
The temporal arc of retina left beyond the radius of zone II is zone III.
Extent of involvement
Extent of involvement is denoted by the clock hours of retinal involvement in the particular zone (Fig. 12.17).
284	Section 3   Diseases of Eye












A	B	C












D	E
Fig. 12.16 Stages of retinopathy of prematurity (ROP):A, stage 1—demarcation line; B, stage 2—demarcation ridge; C, stage 3—extraretinal neovascularization and proliferation; D, stage 4b—subtotal retinal detachment involving macula: E. stage 5—total retinal detachment


Other features
Plus disease refers to presence of engorged veins and tortuous arteries in at least two quadrants at posterior pole with any stage of ROP.
Associated with it is the engorgment and dilatation of iris vessels, which result in poor pharmacological dilatation of pupil. Plus diseases signifies a tendency to progression and is notated by adding plus sign (+) after the number of stage of ROP (e.g., stage 2+)
Pre-plus disease is labelled when venous dilation and arterial tortuosity is more than normal but insufficient to be defined as plus disease.
Aggressive posterior ROP (AP-ROP), also called Rush-disease, refers to the ROP located in zone I with plus disease out of proportion to the peripheral retinopathy or ROP in posterior zone II with severe plus disease. APROP requires immediate treatment. It may progress rapidly to stage 5 ROP without passing through the other stages.
Threshold disease refers to stage 3 +ROP with plus disease located in zone I or II and involving 5 continuous or 8 discontinuous clock hours. This stage needs laser therapy in less than 72 hours.


















Fig. 12.17 Division of retina into zones (I, II, III) and clock hour positions to depict involvement in retinopathy of prematurity.

Prethreshold disease. Early treatment of retinopathy of prematurity (ETROP) group has classified prethreshold disease into two types:
Chapter 12	Diseases of Retina	285



Type I or high-risk prethreshold disease, which needs laser photocoagulation. It includes:
• Zone I Plus disease, any stage,
• Zone I: Non–plus disease, stage 3, and • Zone II: Plus disease, stage 2, and 3.
Type 2 or low-risk prethreshold disease which requires weekly follow-up. It includes:
• Zone I: Non-plus disease, stage 1, and 2, and • Zone II: Non-plus disease stage 3.
Differential diagnosis
• Active ROP needs to be differentiated from familial exudative vitreoretinopathy (FEVR) and incontinentia pigmenti in girls and persistent fetal vasculature.
• Advanced retrolental fibroplasia needs to be differentiated from other causes of leukocoria (see page 306).
Management
Treatment of well-established disease is unsatisf-actory. Prophylaxis is thus very important. To reduce high-risk ROP, the premature newborns should not
be placed in incubator with an O2 concentration of
more than 30% and efforts should be made to avoid infections and attacks of apnoea.Early diagnosis and treatment is essential to prevent blindness in high-risk cases. Therefore, a regular screening and timely intervention is recommended.
Screening protocol
All premature babies born at less than or equal to 32 weeks of gestational age and those weighing 1500 g or less (for Indian scenario <35 weeks and < 2800 g) should be screened for ROP.
■First examination by indirect ophthalmosocpy should be done between 4 to 6 weeks postnatal age or 34 weeks postconceptual age (whichever is earlier). Further line of action will depend upon the status of retina.
• Immature retina is labelled when the vessels are short of one disc diameter of the nasal or temporal ora but ROP is not developed yet.
• ROP, when present should be classified as its stage, zone, and extent of involvement.
Subsequent follow-up examination. Spontaneous regression of disease occurs in about 80% of the cases. So following patients should be examined as below till regression occurs or disease reaches treatment stage:
• Immature retina but no ROP-bi-weekly
• Stage 1 & 2 (Zone I & II ROP), weekly and • Stage 3 (Zone II ROP) also weekly.


Treatment protocol
Treatment options include laser therapy or cryotherapy. ETROP group has recommended use of laser over the cryotherapy.
Laser treatment. Laser photocoagulation using diode laser 810 nm or frequency doubled Nd: YAG (532 nm) with LIO (laser indirect ophthalmoscope) delivery should be carried out in all patients with high-risk pre-threshold, threshold, and aggressive posterior ROP. Post-laser treatment and follow-up. Antibiotic and steroid eye drops should be prescribed for a week. Post-laser treatment follow-up should be done weekly for 3 weeks and if required retreatment should be done. Subsequent follow-up examination should be continued at 3, 6 and 12 weeks after treatment. Long-term follow-up is must for timely management of complications if any.
Surgical treatment. Patients with stage IV a, IV b, and V require lens sparing vitrectomy along with endolaser photocoagulation, and retinal reattachment measures.
PRIMARY RETINAL TELANGIECTASIA
Primary retinal telangiectasia refer to idiopathic congenital or acquired retinal vascular malfor-mations. Characterized by irregular dilation of capillary bed and segmental dilation of neighbouring venules and arterioles. Primary retinal telangiectasia include:
• Idiopathic juxtafoveolar retinal telangiectasia, • Coats’ disease, and
• Leber’s miliary aneurysm.

Idiopathic juxtafoveolar retinal telangiectasia Idiopathic juxtafoveolar retinal telangiectasia also known as ‘idiopathic macular telangiectasia’ is a rare condition presenting with mild decrease in visual acuity due to exudation from the juxtafoveal telangiectatic retinal capillaries. This condition has been divided into three groups: 1, 2 and 3, (each group is subdivided into A and B) depending on the characteristics of lesion.
Coats’ disease
Coats’ disease, also known as exudative retinopathy of Coats, is a severe form of retinal telangiectasia (idiopathic congenital vascular malformation). Characteristic features of Coats’ disease are:
• Typically affects one eye of boys in their first decade of life.
• In early stages it is characterised by large areas of intra and subretinal yellowish exudates and haemorrhages associated with overlying dilated
286	Section 3   Diseases of Eye



and tortuous retinal blood vessels and a number of small aneurysms near the posterior pole and around the disc.
• It may present with visual loss, strabismus or leukocoria (whitish pupillary reflex) and thus needs to be differentiated from retinoblastoma.
• Condition usually progresses to produce exudative retinal detachment and a retrolental mass. In late stages complicated cataract, uveitis and secondary glaucoma occur, which eventually end in phthisis bulbi.
• FFA highlights abnormal vessels, leakage and areas of capillary drop out.
Treatment is as below:
• Photocoagulation or cryotherapy may check progression of the disease if applied in the early stage.
• However, once the retina is detached the treatment becomes increasingly difficult and success rate declines to 33%.
Leber’s miliary aneurysms
• Leber’s miliary aneurysm is essentially a localised less severe form of Coats’ disease presenting in adults with decreased vision.
• Characterized by a local area of fusiform and saccular aneurysmic dilation of venules and arterioles with associated local exudation.
• Treatment consists of direct photocoagulation of the abnormal vessels.
OCULAR ISCHAEMIC SYNDROME
Etiology. Ocular ischaemic syndrome refers to a rare condition resulting from chronic ocular hypoperfusion secondary to >90% stenosis of carotid artery. Carotid stenosis refers to atherosclerotic occlusive carotid artery disease often associated with ulceration at the bifurcation of common carotid artery.
Risk factorsfor carotid stenosis include male gender, old age (60–90 years), smoking, hypertension, diabetes mellitus and hyperlipidaemia. Manifestations of carotid occlusive disease include: • Amaurosis fugax (transient retinal ischaemic
attack),
• Retinal artery occlusion (due to embolus),
• Transient cerebral ischaemic attacks (TIA), and • Stroke.
Clinical features. Ocular ischaemic syndrome is usually unilateral (80%), affecting elder males more commonly than females (2:1).

Symptoms include:
■Loss of vision, which usually progresses gradually over several weeks or months.
■Transient black outs (amaurosis fugax) may be noted by some patients.
■Pain, ocular or periorbital, may be complained by some patients.
■Delayed dark adaptation may be noted by few patients.

Signs include:
■Cornea may show oedema and striae.
■Anterior chamber may reveal faint aqueous flare with few, if any, cells (ischaemic pseudoiritis).
■Pupil may be mid dilated and poorly reacting. ■Iris shows rubeosis iridis (in 66% cases) and
atrophic patches.
■Cataract may occur as a complication in advanced cases.
■Neovascular glaucoma is a frequent sequelae to anterior segment neovascularization.
■Fundus examination may reveal:
• Venousdilatation with irregular calibre but no or only mild tortuosity.
• Retinal arterial narrowing is present.
• Retina shows midperipheral dot and blot haemorrhages, microaneurysms and cotton wool spots.
• Retinal neovascularization is noted in 37% cases, which may be in the form of NVD and occasionally NVE.
• Macular oedema is a common complication. Differential diagnosis. Ocular ischaemic syndrome needs to be differentiated from non-ischaemic CRVO, diabetic retinopathy, hypertensive retinopathy and aortic arch disease caused by Takayasu arteritis, aortoarteritis, atherosclerosis and syphilis (Table 12.1).
Investigations. In suspected cases the carotid stenosis can be confirmed by Doppler ultrasound and magnetic resonance angiography.
Treatment of ocular ischaemic syndrome includes: • Treatment of neovascular glaucoma (see page 250). • Treatment of proliferative retinopathyby panretinal
photocoagulation (PRP) (see page 281).
• Treatment of pseudoiritis with topical steroid eye drops.
• Treatment of carotid stenosis is medical (antiplatelet therapy, oral anticoagulants) and surgical (carotid endarterectomy).
Chapter 12	Diseases of Retina	287


Table 12.1 Differential diagnosis of ocular ischaemic syndrome


Condition
1.  Nonischaemic CRVO


2.  Diabetic retinopathy

3.  Hypertensive retinopathy
4.  Aortic arch disease

Similarities
Unilateral retinal haemorrhages, venous dilatation and cotton wool spots


Microaneurysms, dot and blot haemorrhages, venous dilatation, NVD and NVE, cotton wool spots
Arteriolar narrowing and focal constriction, retinal haemorrhages and cotton wool spots
Arteriolar narrowing, retinal haemorrhages, cotton wool spots, NVD and NVE

Differences
Veins are more tortuous, haemorrhages are more numerous, normal retinal arteriolar perfusion, disc oedema, and sometimes opticociliary shunt vessels can be seen on the disc.
Usually bilateral, with characteristic hard exudates


Usually bilateral, no marked venous changes, and NVD and NVE.
Usually bilateral, absent arm and neck pulses, cold hands, and spasm of arm muscles with excercise.




DYSTROPHIES AND DEGENERATIONS OF RETINA

RETINAL DYSTROPHIES

Hereditary retinal dystrophies primarily affect the outer retina (RPE and photoreceptors). Common retinal dystrophies can be classified as below:
A. Generalised photoreceptor dystrophies
These involve the entire retina (peripheral retina more than macula) and include:
• Typical retinitis pigmentosa and its variants, • Progressive cone dystrophy,
• Leber congenital amaurosis,
• Congenital stationary night blindness, and
• Congenital monochromatism (achromatopsia).
B. Macular dystrophies
These primarily involve the macular area and a few common macular dystrophies are:
• Juvenile best macular dystrophy, • Stargardt’s disease, and
• Vitelliform dystrophy.
Note. Only the most important retinal dystrophy, the retinitis pigmentosa and its varients, are described here.
RETINITIS PIGMENTOSA
Retinitis pigmentosa, primary pigmentary retinal dystrophy is a hereditary disorder predominantly affecting the rods more than the cones.
Inheritance
Retinitis pigmentosa (RP) may occur as:
1. Sporadic disorder, isolated without family history due to mutation of multiple gene (>50%) including rhodopsin gene (40%), or

2. Inherited disorder as:
• Autosomal recessive (AR), most common (25%), intermediate severity
• Autosomal dominant (AD), next common (25%), least severe
• X-linked (XL), least common (10%), most severe.
Prevalence and demography
• Prevalence. It occurs in 1 person per 5,000 of the world population.
• Age. It appears in the childhood and progresses slowly, often resulting in blindness in advanced middle age.
• Race. No race is known to be exempt or prone to it. • Sex. Males are more commonly affected than
females in a ratio of 3:2.
• Laterality. Disease is almost invariably bilateral and both eyes are equally affected.
Pathogenesis
As a group majority of retinitis pigmentosa conditions are characterized bydeath of rod photoreceptors. The molecular mechanism by which the genetic mutation eventuallycausesrod celldeathare unclear, although ample evidence indicates that apoptosis is involved in the final pathway of cell death. That the cone photoreceptors ultimately die from a disease that begins with rod-cell disease remains a puzzle.

Clinical features
Typical retinitis pigmentosa, i.e., rod-cone dystrophy, in which rods are degenerated early and cones are involved late, is characterized by following features:
A. Visual symptoms
1. Night blindness. It is the characteristic and earliest feature and may present several years before the visible changes in the retina appear. It occurs due to degeneration of the rods.
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2. Dark adaptation. Light threshold of the peripheral retina is increased; though the process of dark adaptation itself is not affected until very late.
3. Tubular vision, i.e., loss of peripheral vision with preservation of central vision occurs in advanced cases.
4. Central vision is also lost ultimately after many years.
B. Fundus changes (Fig. 12.18)
1. Retinal pigmentary changes. These are typically perivascular (around veins) and jet black spots resembling bone corpuscles in shape. Initially, these changes are found in the equatorial region only and later spread both anteriorly and posteriorly.
2. Retinal arterioles are attenuated (narrowed) and may become thread-like in late stages.
3. Thinning and atrophy of retinal pigment epithelium (RPE) is seen in mid and far peripheral retina with relative sparing of RPE at the macula.
4. Optic disc becomes pale and waxy in later stages and ultimately consecutive optic atrophy occurs (Fig. 12.18).
5. Other associated changes which may be seen are colloid bodies, choroidal sclerosis, cystoid macular oedema, atrophic or cellophane maculopathy.
C. Visual field changes
Annular or ring-shaped scotoma (Fig. 12.19) is a typical feature which corresponds to the degenerated




















Fig. 12.18 Fundus picture of retinitis pigmentosa with
consecutive optic atrophy

equatorial zone of retina. As the disease progresses, scotoma increases anteriorly and posteriorly and ultimately only central vision is left (tubular vision). Eventually, even this is also lost and the patient becomes blind.
D. Electrophysiological changes
Typical electrophysiological changes appear early in the disease before the subjective symptoms or the objective signs (fundus changes) appear.
1. Electroretinogram (ERG) is initially subnormal (scotopic affected before photopic; b-wave affected before a wave) and eventually extinguished.
2. Electro-oculogram (EOG) is subnormal with an absence of light peak.
Associations of retinitis pigmentosa
I. Ocular associations. These include myopia, primary open-angle glaucoma, microphthalmos, conical cornea (keratoconus) and posterior subcapsular cataract.
II. Systemic associations. Most cases of retinitis pigmentosa (RP) are isolated (i.e., with no systemic features), but about 25% have associated systemic diseases. A number of specific syndromes are described: 1. Laurence-Moon-Biedl syndrome. It is characterised by retinitis pigmentosa, obesity, hypogenitalism,
polydactyly and mental deficiency.
2. Cockayne’s syndrome. It comprises retinitis pigmentosa, progressive infantile deafness, dwarfism, mental retardation, nystagmus and, ataxia.




















Fig. 12.19 Field changes in retinitis pigmentosa
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3. Refsum’s syndrome. It is characterised by retinitis pigmentosa, peripheral neuropathy and cerebellar ataxia.
4. Usher’s syndrome. It includes retinitis pigmentosa and labyrinthine deafness.
5. Hallgren’s syndrome. It comprises retinitis pigmentosa,vestibulocerebellarataxia,congenital deafness and mental deficiency.
6. Other associated syndromes include Bussen– Koranzweig syndrome (Abetalipoproteinaemia), Kearns-Sayer syndrome, Friedreich’s ataxia, Bardet-Biedle syndrome, NARP (neuropathy, ataxia, and retinitis pigmentosa), neuronal ceroid lipofuscinosis, and olivopontocerebellar degeneration.
Atypical forms of retinitis pigmentosa
1. Cone-rod dystrophy. In this condition, cones are degenerated earlier and more severely than the rods.
Symptoms include:
• Central vision is reduced, • Colour vison is defective,
• Defective vision in bright light
Fundus examination shows macular lesions with or without peripheral changes.
2. Retinitis pigmentosa sine pigmento. It is characterised by all the clinical features of typical retinitis pigmentosa, except that there are no visible pigmentary changes in the fundus.
3. Sectorial retinitis pigmentosa. It is characterized by involvement of only one sector of the retina.
4. Pericentric retinitis pigmentosa. In this condition, all the clinical features are similar to typical retinitis pigmentosa except that pigmentary changes are confined to an area, immediately around the macula.
5. Retinitis punctata albescens. It is characterised by the presence of innumerable discrete white dots scattered over the fundus without pigmentary changes. Other features are narrowing of arterioles, night blindness and constriction of visual fields.
Treatment
It is most unsatisfactory; rather we can say that till date there is no effective treatment for the disease. 1. Measures to stop progression, which have
been tried from time to time, without any breakthrough include: vasodilators, placental extracts, transplantation of rectus muscles into

suprachoroidal space, light exclusion therapy, ultrasonic therapy and acupuncture therapy. Recently vitamin A (15000 IU, PO, qd of palmitate form) has been recommended to check its progression.
2. Correct any refractive error, prescribe glasses.
3. Systemic acetazolamide (500mg po) for associated cystoid macular oedema.
4. Low vision aids (LVA) in the form of ‘magnifying glasses’ and ‘night vision device’ may be of some help.
5. Rehabilitation of the patient should be earned out as per his socioeconomic background.
6. Prophylaxis.Genetic counselling for no consan-guinous marriages may help to reduce the inci-dence of disease. Further, affected individuals should be advised not to produce children.

RETINAL DEGENERATIONS

Retinal degenerations are acquired disorders of retina characterized by degenerative changes. These can be classified as below:
■Peripheral retinal degenerations, ■Vitreoretinal degenerations, and ■Macular degenerations, e.g.,
• Age-related degeneration (see page 295), and • Myopic macular degeneration (see page 41).
PERIPHERAL RETINAL DEGENERATIONS
1. Lattice degeneration. It is the most important degeneration associated with retinal detachment. Incidence is 6 to 10% in general population and 15 to 20% in myopic patients.
Characteristic feature includes:
• White arborizing lines arranged in a lattice pattern along with areas of retinal thinning and abnormal pigmentation (Fig. 12.20A).
• Small round retinal holes are frequently present in it.
• Typical lesion is spindle-shaped, located between the ora serrata and the equator with its long axis being circumferentially oriented.
• Involves more frequently the temporal than the nasal, and is superior than the inferior halves of the fundus.
2. Snail tract degeneration. It is a variant of lattice degeneration in which white lines are replaced by snow-flake areas which give the retina a white frost-like appearance (Fig. 12.20 B).
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Fig. 12.20  Peripheral retinal degenerations: A, lattice degeneration; B, snail track degeneration; C, acquired retinoschisis; D, white­with­pressure; E, focal pigment clumps; F, diffuse chorioretinal degeneration; and G, peripheral cystoid degeneration

3. Acquired retinoschisis. The term retinoschisis refers to splitting of the sensory retina into two layers at the level of the inner nuclear and outer plexiform layers. It occurs in two forms—the congenital and acquired.
Acquired retinoschisis is also called as senile retinoschisis, may rarely act as predisposing factor for primary retinal detachment. It is characterised by thin, transparent, immobile, shallow elevation of the inner retinal layers (Fig. 12.20C) which typically produces absolute field detects—the fact which helps in differentiating it from the shallow retinal detachment which produces a relative scotoma. The condition is frequently bilateral and usually involves the lower temporal quadrants, anterior to the equator.
4. White-with-pressure and white-without pressure. These are not uncommonly associated with retinal detachment.
• ‘White-with-pressure’ lesions are characterised by greyish translucent appearance of retina seen on scleral indentation (Fig. 12.20D).
• ‘White-without-pressure’ lesions are located in the peripheral retina and may be associated with lattice degeneration.
5. Focal pigment clumps. These are small, localised areas of irregular pigmentation, usually seen in the equatorial region (Fig. 12.20E). These may be associated with posterior vitreous detachment and/ or retinal tear.

6.Diffuse chorioretinal degeneration.It is characterised by diffuse areas of retinal thinning and depigmentation of underlying choroid (Fig. 12.20F). It commonly involves equatorial region of highly myopic eyes.
7. Peripheral cystoid retinal degeneration. It is a common degeneration (Fig. 12.20G) seen in the eyes of old people. It may predispose to retinal detachment in some very old people.
VITREORETINAL DEGENERATIONS Vitreoretinal degenerations or vitreoretinopathies include:
• Wagner’s syndrome, • Stickler syndrome,
• Favre-Goldmann syndrome,
• Familial exudative vitreoretinopathy, • Erosive vitreoretinopathy,
• Dominant neovascular inflammatory vitreoretino-pathy, and
• Dominant vitreoretinochoroidopathy.
Note. Characteristic features of some conditions are mentioned here.
Wagner’s syndrome
Wagner’s syndrome has an autosomal dominant (AD) inheritance with following features:
• Vitreous is liquified with condensed membranes. • Retina shows narrow and sheathed vessels, and
pigmented spots in the periphery. • Choroid may be atrophied.
• Cataract may develop as late complication.

Stickler syndrome
Stickler syndrome, also known as hereditary arthro-ophthalmopathy, is an autosomal dominant connective tissue disorder characterized by following features:
Ocular features are as below:
Vitreous is liquified and shows syneresis giving appearance of an optically-empty vitreous cavity. Progressive myopia is very common.
Radial lattice like degeneration associated with pigmentary changes and vascular sheathing. Bilateral retinal detachment may occur in 30% cases (commonest inherited cause of retinal detachment in children).
Ectopia lentis is occasionally associated. Pre-senile cataract occurs in 50% cases.
Orofacial abnormalities include flattened nasal bridge, maxillary hypoplasia, cleft palate and high arched palate.
Chapter 12	Diseases of Retina	291



Arthropathy is characterized by stiff, painful, prominent and hyperextensible large joints.
Other features include deafness and mitral valve prolapse.
Favre-Goldmann syndrome
It is an autosomal recessive condition presenting in childhood with nyctalopia. Characteristic features are:
• Vitreous shows syneresis but the cavity is not optically empty.
• Retinoschisis, both central (affecting macula) and peripheral, is present, although macular findings are more subtle.
• Pigmentary changes similar to retinitis pigmentosa are marked.
• ERG is subnormal.

MACULAR DISORDERS

Macula, being concerned with vision, has attracted the attention of many retina specialists. Consequently, many disorders have been defined and variously classified. A simple, etiological classification for a broad overview of the macular lesions is as follows: A. Congenital anomalies. These include aplasia, hypoplasia and coloboma.
B. Hereditary dystrophies. These include Best’s disease, Stargardt’s disease, butterfly-shaped dystrophy, bull’s eye dystrophy and central areolar dystrophy.
C. Acquired maculopathies include:
1. Traumatic lesions. These include traumatic macular oedema, traumatic macular degeneration, macular haemorrhage and macular hole (see page 431).
2. Inflammations, i.e., central chorioretinitis (see page 162).
3. Solar retinopathy, i.e., photoretinitis.
4. Degenerations. Important conditions are age-related macular degeneration (ARMD), and myopic degeneration.
5. Metabolic disorders include: diabetic maculopathy and sphingolipidosis.
6. Toxic maculopathies. These are chloroquine and phenothiazine-induced maculopathy.
7. Miscellaneous acquired maculopathies. A few common conditions are:
• Central serous chorioretinopathy (CSCR), • Cystoid macular oedema (CME),
• Macular hole,
• Macular epiretinal membrane,

• Vitreomacular traction syndrome, and
• Idiopathic choroidal neovascularization. Note. Only a few macular disorders are described.
HEREDITARY MACULAR DYSTROPHIES Best’s disease
Inheritence: Autosomal dominant
Clinical picture can be divided into five stages:
• Pre-vitelliform stage. Normal fundus, but EOG is abnormal.
• Vitelliform stage. Egg yolk lesion at macula.
• Pseudohypopyon stage. Partially absorbed egg yolk lesion.
• Vitelli eruptive stage. A scrambled egg appearance of macula.
• Stage of scarring. Hypertrophic or atrophic vascu-larized scar at macula.
Stargardt’s disease
Clinical presentation is with decreased vision in first or second decade of life.
Fundus examinationshows ‘beaten-bronze’ or ‘snail-slime reflex’ in macular area.
SOLAR RETINOPATHY
Solar retinopathy also known as photoretinitis, or eclipse retinopathy, refers to retinal injury induced by direct or indirect sun viewing. Solar retinopathy is associated with religious sun gazing, solar eclipse observing, telescopic solar viewing, sun bathing and sun watching in psychiatric disorders.
Causes of photic retinopathy, other than solar retinopathy, are:
• Welding arc exposure,
• Lightening retinopathy, and
• Retinal phototoxicity from ophthalmic instruments like operating microscope.
Pathogenesis
Solar radiations damage the retina through: ■Photochemical effects produced by UV and visible
blue light, and
■Thermal effects may enhance the photochemical effects. The long visible wavelength and infrared rays from the sun are absorbed by the pigment epithelium producing a thermal effect. Therefore, severity of lesion varies directly with the degree of pigmentation of the fundus, duration of exposure and the climatic conditions during exposure.
Clinical features Symptoms. These include:
• Persistence of negative after-image of the sun, progressing later into a positive scotoma and metamorphopsia.
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• Decreased vision (6/12–6/60) (unilateral or bilateral) which develops within 1 to 4 hours after solar exposure, usually improves to 6/6–6/12 within six months.
Signs. Initially, the fundus may appear normal. Shortly after exposure a small yellow spot with grey margin may be noted in the foveolar and parafoveolar region. The typical lesion, which appears later, consists of a central burnt-out hole in the pigment epithelium surrounded by aggregation of mottled pigment. Ophthalmoscopically, it appears as a bean- or kidney-shaped pigmented spot with yellowish white centre in the foveal region. In worst cases, typical macular hole may appear.
Treatment
There is no effective treatment for photoretinitis, so emphasis should be on prevention. Eclipse viewing should be discouraged unless there is proper use of protective eye wear filters (which absorb UV and infrared wavelengths).
Prognosis is guarded, since some scotoma and loss in visual acuity by one or two lines mostly persists.
CENTRAL SEROUS CHORIORETINOPATHY Central serous chorioretinopathy (CSCR) is characterised by spontaneous serous detachment of neurosensory retina in the macular region, with or without retinal pigment epithelium detachment.
Etiopathogenesis Risk factors include:
• Age and sex. The disease affects typically young adult (20–50 years), males more than females,
• Personality. Type A personality individuals are more prone,
• Steroid intake is an important risk factor, • Emotional stress,













Fig. 12.21 Best disease: vitelliform disease (egg yolk lesion at macula)

• Hypertension,
• Pregnancy (usually 3rd trimester), and
• Cushing’s disease are also reported as risk factors. Pathogenesis is not known exactly. Various theories have been postulated. Presently, the most accepted theory is of ‘choroidal vascular hyperpermeability’. This theory correlates the clinical findings with indocyanine green (ICG) angiography findings. It proposes that sympathetic drive, sympathomimetics and corticosteroids alter the choroidal vascular permeability either directly or indirectly by affecting its autoregulation. This, in turn, increases the tissue hydrostatic pressure in the choroid causing pigment epithelial defect (PED) resulting in a breach in the outer blood retinal barrier. Leakage of fluid across this area results in development of localized serous detachment of neurosensory retina.
Clinical features
Symptoms. Patient may present with:
• Sudden painless loss of vision (6/9–6/24) associated with
• Relative positive scotoma, micropsia and metamorphopsia.
Signs. Biomicroscopic fundus examination reveals: • Mild elevation of macular area, demarcated by a
circular ring reflex.
• Small yellow grey elevations may be seen due to RPE detachment.
• Foveal reflex is absent or distorted (Fig. 12.22). • Subretinal deposists may be seen.
• Multifocal pigmentary changes suggest chronicity.

Clinical course
CSR is usually self-limiting but often recurrent. Three patterns are known:















Fig. 12.22 Fundus photograph showing central serous retinopathy
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Acute classic CSCR is characterized by short clinical course with spontaneous resolution within 3–6 months with near normal visual recovery. Recurrences are known in 30–50% of all the cases. Chronic CSCR, also termed as diffuse retinal pigment epitheliopathy (DRPE), is seen in few cases. It is characterized by a chronic course lasting more than 12 months, typically affecting individuals above 50 years of age. Such cases may have permanent visual impairment due to progressive RPE atrophy and photoreceptor degeneration.
Bullous CSCR is rare presentation characterized by larger and more numerous areas of serous retinal and RPE detachments often confused with bullous retinal detachment.
Investigations
1.Fundus fluorescein angiography helps in confirming the diagnosis. Two patterns of progressive leakage and pooling from one or more points seen are:
• Ink-blot pattern. It consists of small hyperfluorescent spot which gradually increases in size (Fig. 12.23A).
• Smoke-stack pattern. It consists of a small hyperfluorescent spot which ascends vertically like a smoke-stack and gradually spreads laterally to take a mushroom or umbrella configuration (Fig. 12.23B).
2.ICGshows multiple areas of hyperfluorescence due to choroidal hyperpermeability.
3. OCT shows neurosensory retinal detachment and accompanying small detachments of the RPE (Fig. 12.23C).
Differential diagnosis
Differential diagnosis of CSR includes other entities which may produce serous detachment of sensory retina in macular area. These include optic pit, idiopathic polypoidal choroidal vasculopathy, macular hole with serous detachment, choroidal tumors and pigment epithelial defect (PED).
Treatment
1. Conservative measures. Reassurance is the only treatment required in majority of the cases, since CSR undergoes spontaneous resolution in 80 to 90% cases. Visual acuity returns to normal or near normal within 3 to 6 months.
• Discontinuation of steroids, if possible, should be done at the earliest.
• Life style changes to reduces stress in life, should be adopted.
2. Laser photocoagulation is indicated in following cases:













A













B







C
Fig. 12.23  Fundus fluorescein angiogram showing ink­blot pattern (A) and smoke­stack pattern (B) of hyperfluorescence in central serous retinopathy and (C) OCT picture of CSR

• Long-standing cases (more than 6 months).
• Patients having recurrent CSR with visual loss.
• Patients having permanent loss of vision in the other eye due to this condition. Contraindications include the cases having leak near or within the FAZ.
3. Photodynamic therapy (PDT) may be beneficial for those with severe disease not amenable to conventional laser treatment, e.g., with sub-foveal leaks and chronic cases.
4. Anti-VEGF can be considered if CNV develops.
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CYSTOID MACULAR OEDEMA (CME)
It refers to collection of fluid in the outer plexiform (Henle’s layer) and inner nuclear layer of the retina, centred around the foveola.
Etiology
It is associated with a number of disorders. A few common causes are as follows:
1.  Complication of ocular treatment such as:
• Ocular surgery, e.g., cataract extraction (Irvine-Gass syndrome), penetrating keratoplasty, glaucoma filteration surgery and retinal detachment surgery.
• Ocular laser therapy, e.g., panretinal photoco-agulation (PRP), and Nd:YAG laser capsulotomy.
• Topical ocular therapy with eye drops like epinephrine, dipivefrine and prostaglandin analogues, especially in patients who have undergone cataract surgery.
2. Retinal vascular disorders e.g., diabetic retinopathy and central retinal vein occlusion (CRVO), branch retinal vein occlusion (BRVO), retinal telangiectasia (e.g., Coats’ disease), periphlebitis retinae (Eales disease), and hypertensive retinopathy.
3. Intraocular inflammations, e.g., pars planitis, posterior uveitis and anterior uveitis.
4. Retinal dystrophies, e.g., retinitis pigmentosa.
5. Vitreomacular traction as seen in macular epiretinal membrane (ERM) and vitreo macular traction (VMT) syndrome.
6. Systemic diseases such as leukaemia, chronic renal failure and multiple myeloma.
7. Miscellaneous causes include intraocular tumours, choroidal neovascularization (CNV) and collagen vascular diseases.
Pathogenesis
CME develops due to leakage of fluid following breakdown of inner blood-retinal barrier (i.e., leakage from the retinal capillaries) and accumulating in the outer plexiform and inner nuclear layer of retina with the formation of cyst-like changes as depicted on OCT macular scan (Fig. 12.25B).
Clinical features
1. Visual loss. Initially there is minimal to moderate loss of vision, unassociated with other symptoms. If oedema persists, there may occur permanent decrease in vision.
2. Ophthalmoscopy reveals loss of foveal contour, retinal thickening, a yellow spot at the center of fovea and in clinically established cases a typical ‘Honey-comb appearance’ of macula (due to multiple cystoid














Fig. 12.24 Fundus photograph showing honey­comb appearance in cystoid macular oedema (CME)

oval spaces) (Fig. 12.24). CME is best examined with a fundus contact lens on slit-lamp or +90D lens. Associated features depend on the underlying cause, e.g., CRVO, etc.
3. Fundus fluorescein angiography demonstrates leakage and accumulation of dye in the macular region which in a well-established case presents a ‘flower petal appearance’ in late frames (Fig. 12.25A).
4. Optical coherence tomography (OCT) reveals loss of foveal depression, intraretinal area of decreased reflectivity with round optically clear regions (cystoid spaces) and over all retinal thicknening (Fig. 12.25B). Detection rate on OCT is similar to FFA. It can also detect associated specific pathology, e.g., vitreomacular traction.
Complications
Long-standing CME may end in lamellar macular hole.
Treatment
1. Treatment of the causative factor,e.g., photocoagula-tion for diabetic CSME; cessation of causative topical 2% adrenaline eye drops and soon.
2. Topical antiprostaglandin (NSAID) drops like ketorolac, diclofenac or profenac when used pre-and postoperatively, prevent the occurrence of CME associated with intraocular surgery. These are also useful in the treatment of most CMEs when given for 3 to 4 months.
3. Topical and systemic steroids may be of some use in established cases.
4. Systemic carbonic anhydrase inhibitors (CAIs), e.g., oral acetazolamide may be beneficial in some cases of CME, e.g., in retinitis pigmentosa.
Chapter 12	Diseases of Retina	295















A










B
Fig. 12.25 Cystoid macular oedema: A, Fundus fluorescein angiogram showing flower petal appearance and B, OCT picture showing cystoid spaces

AGE-RELATED MACULAR DEGENERATION Age-related macular degeneration (ARMD), also called senile macular degeneration, is a bilateral disease of persons over 50 years of age. It is a leading cause of blindness in developed countries, in population above the age of 65 years. It is of two types non-exudative and exudative.
Etiopathogenesis
ARMD is an age-related disease of worldwide prevalence. Certain risk factors which may affect the age of onset and/or progression include heredity, nutrition, smoking, hypertension, exposure to sun light, hyperopia, blue eyes and cataract particularly nuclear opacity. The disease is most prevalent in Caucasians.
Clinical types
1. Non-exudative or atrophic ARMD
It is also called dry or geographic ARMD and is responsible for 90% cases.
Symptoms. It typically causes mild to moderate, gradual loss of vision. Patients may complain of distorted vision and difficulty in reading due to central shadowing.

Signs. Ophthalmoscopically, lesions of non exudative ARMD can be described into three stages (Fig. 12.26A):
Early stage cases are characterized by occurrence of macular drusens, focal hyperpigmentation and pale area of retinal pigment atrophy (RPE atrophy). Macular drusens are well defined, yellowish white, slightly-elevated spots. In early cases less than 20 small to medium sized (60–125 mm) drusens are seen.
Intermediate stagecasesshow sharply circumscribed circular areas of RPE atrophy with variable loss of choriocapillaries along with drusens [1 large drusen >125mm and/or >20 medium drusens (60–125 mm)]. Large drusens are soft drusens with less sharply defined edges, tend to enlarge or coalesce. Advanced stage cases show enlargement of atrophic areas within which the larger choroidal vessels may become visible and pre-existing drusen disappear (Geographical atrophy).
2. Exudative ARMD
It is also called wet or neovascular ARMD. It is responsible for only 10% cases of ARMD but is associated with comparatively rapidly progressive marked loss of vision.
Typical lesions of exudative ARMD seen in chro-nological order are as below:
• Drusens with retinal pigment epithelial detachment (PED) seen as sharply circumscribed dome-shaped elevation.
• Choroidal neovascularization (CNV) proliferating in sub-RPE space (type 1) is seen as greyish green or pinkish yellow raised lesion (Fig 12.26B). The CNV proliferating in sub-retinal space (type 2) is seen as sub-retinal halo or pigment plaque.
• Haemorrhagic pigment epithelial detachment (PED). It appears as dark elevated mount.
• Haemorrhagic detachment of neurosensory retina which assumes diffuse outline and a lighter red colour around and adjacent to the PED.
• Disciform sub-retinal scarring in the macular region may result from gradual organization of blood with further fibrovascular ingrowth.
Diagnosis
Clinical diagnosis is made from the typical signs described above, which are best elucidated on examination of the macula by slit-lamp biomicroscopy with a +90D/+78D non-contact lens or Mainster contact lens.
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Fundus fluorescein angiography and indocyanine green angiography help in detecting choroidal neovascularization (CNV) in relation to foveal avascular zone. CNV may be classical or occult:
• Classical CNVM is seen as lacy hyperfluorescence with progressive leakage (Fig. 12.26 C). It may be subfoveal, juxtafoveal or extrafoveal in location.
• Occult CNVM isseen as stippled hyperfluorescence (type I) or as late leakage of undetermined source. (type II).
■Optical coherence tomography (OCT) reveals subretinal fluid, intraretinal thickening, choroidal neovascularization and haemorrhages in exudative ARMD (Fig. 12.26 D).
Treatment
Treatment of non-exudative ARMD. Currently, there is no effective treatment that stop progression of dry AMD. Measures to be tried include:
• Dietary supplements and antioxidants. The age-related eye disease study (AREDS) has suggested that use of certain specific antioxidants, vitamins and minerals [vitamin C (500 mg) and vitamin E (400 IU), beta carotene (15 mg), zinc oxide (80 mg) and cupric oxide (2 mg)] could possibly prevent or delay the progression of ARMD.
• Smoking cessation may slow down the progress.
• Amsler grid used regularly allows the patients to detect new or progressive metamorphopsia prompting them to seek ophthalmic advice.
• Refraction with increased near add may be helpful in early cases.
• Low vision aid may be needed in advanced cases of geographical atrophy.
Treatment modalities available for exudative (neovas-cular) ARMD :
Intravitreal anti-VEGF therapy has become the treatment of first choice for all CNV lesions. Anti-VEGFs are injected intravitreally. These include:
• Bevacizumab (Avastin), dose: 1.25 mg, or
• Ranibizumab (Lucentis), dose: 0.5 mg/0.05 ml, or • Pegaptanib (Macugen), dose: 0.3 mg in 90 ml (For
detail see page 458).
Results of anti-VEGF are encouraging in the sense that they improve the vision in 30–40% of cases and stabilize the vision in rest of the cases. However, the effect is short lasting and repeated injections are required at an interval of 1–3 months. VEGF-trap-eye (afibercept), a fusion protein, is reported to be equally effective as standard therapy, but requires fewer injections into the eyes.











A










B










C








D
Fig. 12.26 Age­related macular degeneration: A, non­ exudative; B, exudative; C, FFA showing leakage and lacy pattern in CNVM; D, OCT picture of CNVM

Note. Although anti-VEGF therapy is the preferred strategy for the treatment of CNV, some patients may choose not to undergo an intravitreal procedure. In these cases, options include PDT, TPT, argon laser photocoagulation.
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Photodynamic therapy (PDT) is the treatment of choice after anti-VEGF injections for subfoveal and juxtafoveal classic CNVM. In PDT, vertiporfin, a photosensitizer or light activated dye is injected intravenously. The area of CNVM is then exposed to light from a diode laser source at a wavelength (689 nm) that corresponds to absorption peak of the dye. The light-activated dye then causes disruption of cellular structures and occlusion of CNVM with minimum damage to the adjacent RPE, photoreceptors and capillaries.
Transpupillary thermotherapy (TTT) with a diode laser (810 nm) may be considered for subfoveal occult CNVM. PDT is definitely better than TTT but is very expensive.
Double frequency and YAG 532 nm photocoagulation may be used for extrafoveal choroidal neovascular membrane (CNVM).
Surgical treatment. Submacular surgery to remove CNVM and macular translocation surgery are being evaluated.
MACULAR HOLE
Macular hole refers to a partial thickness of full thickness hole in the neurosensory retina in the foveal region.
Causes
1. Senile or idiopathic (83%), more common in females aged 60–80 years than males (F:M, 3:1).
2. Traumatic macular hole account for (5%) cases. 3. Other causes of macular hole include: cystoid
macular oedema, vitreomacular traction, post-surgical, myopia, post-laser treatment, epiretinal membrane traction and post-inflammatory.
Pathogenesis: Senile macular holes are caused by tractional forces associated with early PVD.
Clinical features
Symptoms include:
• Decreased vision, typically around 6/60 level for a full thickness hole and better for a partial hole.
• Metamorphopsia or distortion of vision may be there.
• Central scotoma may be reported by some patients.
Signs. Based on the fundus appearance (best examined with 78/90D slit-lamp examination), the macular hole can be classified into four stages (Fig.12.27):
Stage 1 or impending hole. It is characterized by absent foveal reflex and a yellow spot (Stage 1A, Fig. 12.27A) or a yellow ring (Stage 1B) in the foveal


region. OCT examination reveals a pseudocyst with a vitreous detachment in stage 1 A (Fig. 12.27B), and progression of the pseudocyst with a break in the outer foveal layer in stage 1B.
Stage 2. A small full thickness hole (Fig. 12.27C) is seen either in the centre of the ring (central) or at the margin of the ring (eccentric). OCTexamination shows a full thickness hole less than 400 mm in size (Fig. 12.27D).
Stage 3. A full thickness hole is seen as round reddish spot surrounded by a grey halo [cuff of sub-retinal fluid (SRF)], but no PVD (Fig. 12.27E). OCT examination shows a full thickness macular hole more than 400 mm in size with partial vitreomacular adhesion/traction (Fig. 12.27F).
Stage 4. Full thickness hole with SRF cuff and complete PVD, i.e., posterior vitreous detachment (seen as Weiss ring) (Fig. 12.27G). OCTexamination confirms a large full thickness hole with posterior vitreous detached from the disc and macula. (Fig. 12.27H).
Management
Differential diagnosis of fundus appearance include:
• Macular pucker (epiretinal membrane) with pseudohole,
• Solar retinopathy,
• Intraretinal cyst (e.g., chronic CME with prominent central cyst) and
• Vitreomacular traction syndrome.
Investigations
1. Fundus fluorescein angiography reveals early foveal hyperfluorescence without leak in the late phase in patients with stage 2 to 4 macular holes.
2. Optical coherence tomography (OCT) (Fig. 12.27) is useful for:
• Differentiating true holes from the lamellar holes and cysts,
• Staging of the macular hole,
• Determining the degree of traction from the epiretinal membrane, and
• Planning the surgery.
Treatment
■Stage 1. Treatment is not recommended as spontaneous hole closure can occur. But close follow-up and observation is required as 50% cases do progress.
■Stage 2 to 4 holes of recent onset (<1 year) with reduced visual acuity (<6/24) should be treated with pars plana vitrectomy with posterior hyaloid
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removal, internal limiting membrane (ILM) peeling and gas or silicon oil tamponade with strict postoperative face down position for 7–14 days.
Prognosis. Anatomical closure is reported in 60–85% of cases. Visual improvement is reported in 70% cases with recent onset holes.
Complications of surgery. A comparatively common complication is occurrence or progression of cataract. Other reported complications include: retinal breaks, retinal detachment, late reopening of the hole, RPE loss under the hole, phototoxicity and endophthalmitis.











A






B











C







D


RETINAL DETACHMENT

Retinal detachment is the separation of neurosensory retina proper from the pigment epithelium. Normally, these two layers are loosely attached to each other with a potential space in between. Hence, actually speaking the term retinal detachment is a misnomer and it should be retinal separation.

Classification
Clinico-etiologically retinal detachment can be classified into three types:











E






F











G







H

Fig. 12.27 Macular hole stages 1, 2, 3, 4: Fundus appearance (A, C, E, G) and OCT pictures (B, D, F, H), respectively
Chapter 12	Diseases of Retina	299



1. Rhegmatogenous or primary retinal detachment, 2. Tractional retinal detachment, and
3. Exudative retinal detachment.

RHEGMATOGENOUS OR PRIMARY RETINAL DETACHMENT
Rhegmatogenous retinal detachment usually associated with a retinal break (hole or tear) through which subretinal fluid (SRF) seeps and separates the sensory retina from the pigmentary epithelium. This is the commonest type of retinal detachment.
Etiology
It is still not clear exactly. The predisposing factors and the proposed pathogenesis is as follows:
A. Predisposing factors include:
1. Age. The condition is most common in 40–60 years. However, age is no bar.
2. Sex. More common in males (M:F—3:2).
3. Myopia. About 40% cases of rhegmatogenous retinal detachment are myopic.
4. Aphakia and pseudophakia. The condition is more common in aphakes and pseudophake than phakes.
5. Retinal degenerations predisposed to retinal detachment are as follows:
• Lattice degeneration,
• Snail track degeneration,
• White-with-pressure and white-without-or occult pressure,
• Acquired or retinoschisis, and • Focal pigment clumps.
6. Trauma. It may also act as a predisposing factor. 7. Senile posterior vitreous detachment (PVD). It is
associated with retinal detachment in about 10% cases.
B. Pathogenesis
Pathogenesis of rhegmatogenous retinal detachment (RRD) is summarized in Fig. 12.28. The retinal breaks responsible for RRD are caused by the interplay between the dynamic vitreoretinal traction and predisposing degeneration in the peripheral retina. Dynamic vitreoretinal traction is induced by rapid eye movements especially in the presence of PVD, vitreous syneresis, aphakia and myopia. Once the retinal break is formed, the liquified vitreous may seep through it separating the sensory retina from the pigment epithelium. As the subretinal fluid (SRF) accumulates, it tends to gravitate downwards. The final shape and position of RD is determined













Fig. 12.28 Flowchart depicting pathogenesis of rhegmatogenous retinal detachment

by location of retinal break (Lincoff’s rule) and the anatomical limits of optic disc and ora serrata.
The degenerated fluid vitreous seeps through the retinal break and collects as subretinal fluid (SRF) between the sensory retina and pigmentary epithelium.
Clinical features
Prodromal symptoms include:
• Dark spots (floaters) in front of the eye (due to rapid vitreous degeneration), and
• Photopsia, i.e., sensation of flashes of light (due to irritation of retina by vitreous movements).
Symptoms of detached retina are as follows:
1. Localised relative loss in the field of vision (of detached retina) is noticed by the patient in early stage which progresses to a total loss when peripheral detachment proceeds gradually towards the macular area.
2. Sudden appearance of a dark cloud or veil in front of the eye is complained by the patients when the detachment extends posterior to equator.
3. Sudden painless loss of vision occurs when the detachment is large and central.
Signs. These are elicited on following examinations:
1. External examination, eye is usually normal.
2. Intraocular pressure is usually slightly lower or may be normal.
3. Marcus Gunn pupil (relative afferent pupillary defect) is present in eyes with extensive RD.
4. Plane mirror examination or Distant Direct ophthalmoscopy reveals an altered red reflex in the pupillary area (i.e., greyish reflex in the quadrant of detached retina).
300	Section 3   Diseases of Eye



5. Ophthalmoscopy should be carried out both direct and indirect techniques. Retinal detachment, is best examined by indirect ophthalmoscopy using scleral indentation (to enhance visualization of the peripheral retina anterior to equator).
• Freshly-detached retina gives grey reflex instead of normal pink reflex and is raised anteriorly (convex configuration). It is thrown into folds which oscillate with the movements of the eye. These may be small or may assume the shape of balloons in large bullous retinal detachment. In total detachment retina becomes funnel-shaped, being attached only at the disc and ora serrata. Retinal vessels appear as dark tortuous cords oscillating with the movement of detached retina.
• Retinal breaks associated with rhegmatogenous detachment are located with difficulty. These look reddish in colour and vary in shape. These may be round, horse-shoe shaped, slit-like or in the form of a large anterior dialysis (Fig. 12.29). Retinal breaks are most frequently found in the periphery (commonest in the upper temporal quadrant). Associated retinal degenerations, pigmentation and haemorrhages may be discovered.
• Vitreous pigments may be seen in the anterior vitreous (tobacco dusting or Shaffer sign), with posterior vitreous detachment.
• Old retinal detachment is characterized by retinal thinning (due to atrophy), formation of subretinal demarcation line (high water marks) due to proliferation of RPE cells at the junction of flat detachment and formation of secondary intraretinal cysts (in very old RD).
6. Visual field charting reveals scotomas corres-ponding to the area of detached retina, which are relative to begin with but become absolute in long-standing cases.
7. Electroretinography (ERG)is subnormal or absent.

8. Ultrasonography confirms the diagnosis. It is of particular value in patients with hazy media especially in the presence of dense cataracts and vitreous haemorrhage.
Complications
Complications usually occur in long-standing cases and include proliferative vitreoretinopathy (PVR), complicated cataract, uveitis and phthisis bulbi.
Treatment
Basic principles and steps of RD surgery are sealing of retinal breaks, reducing the vitreous traction on the retina, and flattening of retina by draining of subretinal fluid and external or internal tamponade.
1. Sealing of retinal breaks. All the retinal breaks should be detected, accurately localised and sealed by producing aseptic chorioretinitis, with cryocoagulation, or photocoagulation or diathermy. Cryocoagulation is more frequently utilised (Fig. 12.30).
2. Drainage of SRF. It allows immediate apposition between sensory retina and RPE. SRF drainage is done very carefully by inserting a fine needle through the sclera and choroid into the subretinal space and allowing SRF to drain away. SRF drainage may not be required in some cases.
3. Maintenance of chorioretinal apposition  is required for at least a couple of weeks. This can be accomplished by either of the following procedures depending upon the clinical condition of the eye:
i. Scleral buckling i.e., inward indentation of sclera to provide external tamponade is still widely used to achieve the above mentioned goal successfully in simple cases of primary RD. Scleral buckling is achieved by inserting an explant (silicone sponge or solid silicone band) with the help of mattress type sutures applied in the sclera (Fig. 12.31).











A	B	C
Fig. 12.29 Retinal detachment associated with: A, horse­shoe tear; B, round retinal hole; C, anterior dialysis
Chapter 12	Diseases of Retina	301

















Fig. 12.30 Cryocoagulation of the retinal hole area under direct vision with indirect ophthalmoscopy
















Fig. 12.31 Diagram depicting scleral buckling and subretinal fluid (SRF) drainage

Radially-oriented explant is most effective in sealing an isolated hole, and circumferential explant (encirclage) is indicated in breaks involving three or more quadrants.
ii. Pneumatic retinopexy is a simple out-patient procedure which can be used to fix a fresh superior RD with one or two small holes extending over less than two clock hour area in the upper two-thirds of peripheral retina. In this technique after sealing the breaks with cryopaxy, an expanding gas bubble
(SF6 or C3 F8) is injected in the vitreous. Then proper
positioning of the patient is done so that the break is uppermost and the gas bubble remains in contact with the tear for 5–7 days.
iii. Pars plana vitrectomy, endolaser photocoagulation and internal tamponade. This procedure is indicated in:

• All complicated primary RDs, and • All tractional RDs.
• Presently, even in uncomplicated primary RDs (where scleral buckling is successful), the primary vitrectomy is being used with increasing frequency by the experts in a bid to provide better results.
Main steps of this procedure are:
• Pars plana, 3-port vitrectomy (see page 261) is done to remove all membranes and vitreous and to clean the edges of retinal breaks.
• Internal drainage of SRF through existing retinal breaks using a fine needle or through a posterior retinotomy is done.
• Flattening of the retina is done by injecting silicone oil or perfluorocarbon liquid.
• Endolaser is then applied around the area of posterior retinotomy, retinal tears, and holes to create chorioretinal adhesions.
• To tamponade the retina internally either silicone oil is left inside or is exchanged with some long-acting gas (gas-silicone oil exchange). Gases commonly used to tamponade the retina are
sulphur hexafluoride (SF6) or perfluoropropane
(C3 F8) (see page 262).
Prophylaxis
Occurrence of primary retinal detachment can be prevented by timely application of laser photo-coagulation or cryotherapy in the areas of retinal breaks and/or predisposing lesions like lattice degeneration. Prophylactic measures are particularly indicated in patients having associated high-risk factors like myopia, aphakia, retinal detachment in the fellow eye or history of retinal detachment in the family.
EXUDATIVE OR SOLID RETINAL DETACHMENT Exudative (serous) retinal detachment occurs due to the retina being pushed away by a neoplasm or accumulation of fluid beneath the retina following inflammatory or vascular lesions.
Etiology
Common causes of exudative retinal detachment can be grouped as under:
1. Systemic diseases. These include: toxaemia of pregnancy, renal hypertension, blood dyscrasias and polyarteritis nodosa.
2. Ocular diseases. These include:
i.  Congenital abnormalities such as nanophthalmos, optic pit, choroidal coloboma and familial exudative vitreoretinopathy (FEVR);
ii. Inflammations such as Harada’s disease,
302	Section 3   Diseases of Eye



sympathetic ophthalmia, posterior scleritis, and orbital cellulitis;
iii.Vascular diseases such as central serous retinopathy and exudative retinopathy of Coats;
iv. Neoplasms, e.g., malignant melanoma of choroid retinoblastoma (exophytic type), haemangioma, and metastatic tumours of choroid;
v.  Sudden hypotony due to perforation of globe and intraocular operations.
vi. Uveal effusion syndrome is characterised by bilateral detachment of the peripheral choroid, ciliary body and retina.
vii. Choroidal neovascularization may also cause exudative retinal detachment.
Clinical features
Exudative retinal detachment can be differentiated from a simple primary detachment by:
• Absence of photopsia, holes/tears, folds and undulations.
• The exudative retinal detachment is smooth and convex (Fig. 12.32). At the summit of a tumour it is usually rounded and fixed and may show pigmentary disturbances.
• Pattern of retinal vessels may be disturbed occasionally, due to presence of neovascularization on the tumour summit.
• Shifting fluid characterised by changing position of the detached area with gravity is the hallmark of exudative retinal detachment.
• On transillumination test a simple detachment appears transparent while solid detachment is opaque.
Investigations
1. Ocular and systemic examination should be carried out thoroughly.













Fig. 12.32 Exudative retinal detachment in a patient with malignant melanoma of choroid

2. B-scan ultrasonography may help delineate the underlying cause.
3. FFA may show source of fluid.
4. CT scanand/or MRI is useful, specially in cases of intraocular tumours.
Treatment
Treatmentof the causeis required in most of the cases, as the exudative retinal detachment due to transudate, exudate and haemorrhage may undergo spontaneous regression following absorption of the fluid. Thus, the treatment should be for the causative disease.
• Enucleation is usually required in the presence of intraocular tumours.
TRACTIONAL RETINAL DETACHMENT
Tractional retinal detachment (TRD) occurs due to retina being mechanically pulled away from its bed by the contraction of fibrous tissue in the vitreous (vitreoretinal tractional bands).
Etiology
TRD is associated with the following conditions:
• Post-traumatic retraction of scar tissue especially following penetrating injury,
• Proliferative diabetic retinopathy,
• Post-haemorrhagic retinitis proliferans, • Retinopathy of prematurity,
• Plastic cyclitis,
• Sickle cell retinopathy,
• Proliferative retinopathy in Eales’ disease, • Vitreomacular traction syndrome,
• Incontinentia pigmenti, • Retinal dysplasia, and
• Toxocariasis.

Clinical features
Photopsia and floaters are not complained. Tractional retinal detachment (Fig. 12.33) is characterised by: • Presence of vitreoretinal bands with lesions of the
causative disease.
• Retinal breaks are usually absent and configuration of the detached area is concave.
• Highest elevation of the retina occurs at sites of vitreoretinal traction.
• Retinal mobility is severely reduced and shifting fluid is absent.
Treatment
• Surgery is difficult and requires pars plana vitrectomy to cut the vitreoretinal tractional bands and internal tamponade with either a long-acting gas or silicon oil.
• Prognosis in such cases is usually not so good.
Chapter 12	Diseases of Retina	303
















Fig. 12.33 Tractional retinal detachment in a patient with advanced diabetic retinopathy

TUMOURS OF RETINA

Tumours of retina have become a subject of increasing interest to clinical ophthalmologists as well as ocular pathologists. Classification of retinal tumours is given below and only a few, which are commonly seen are described.
Classification
A. Primary tumours
1. Neuroblastic tumours. These arise from sensory retina (retinoblastoma and astrocytoma) and pigment epithelium (benign epithelioma and melanotic malignant tumours).
2. Mesodermal  angiomata,  e.g.,  cavernous haemangioma.
3. Phakomatoses. These include: angiomatosis retinae (von Hippel-Lindau disease), tuberous sclerosis (Bourneville’s disease), neurofibromatosis (von Recklinghausen’s disease and encephalo-trigeminal angiomatosis (Sturge-Weber syndrome).
B. Secondary tumours
1. Direct extension, e.g., from malignant melanoma of the choroid.
2. Metastatic carcinomas from the gastrointestinal tract, genitourinary tract, lungs, and pancreas.
3. Metastatic sarcomas.
4. Metastatic malignant melanoma from the skin.
RETINOBLASTOMA
Retinoblastoma is a common malignant tumour arising from the neurosensory retina in one or both eyes.
Demographic data
1. Prevalence. It is the most common intraocular tumour of childhood occurring 1 in 15,000 to 20,000 live births.

2. Age. Retinoblsatoma is confined to infancy and very young children usually seen between 1 and 2 years of age.
3. Sex. There is no sex predisposition.
4. Race. It is rarer in Negroes than Whites.
5. Bilaterality. In 25–30% cases, there is bilateral involvement, although one eye is affected more extensively and earlier than the other.
Genetics and heredity
Retinoblastoma (RB) gene has been identified as 14 band on the long arm of chromosome 13 (13q 14) and is a ‘cancer suppressor’ or ‘antioncogenic’ gene. Deletion or inactivation of both the normal allels of this protective gene by two mutations (Knudson’s two hit hypothesis, 1971) results in occurrence of retinoblastoma.
Some facts about occurrence of retinoblastoma are as below:
■Of all cases, only 10% are familial (inherited by autosomal dominant mode) and the rest about 90% occur sporadically.
■Of sporadic cases, about two-third (i.e., 60% of all cases) occur by somatic mutation and one-third (i.e., 30% of all cases) occur by germline mutation. ■Thus, the retinoblastoma either occurs as heritable (germline) cases (40%) or non-heritable somatic
cases (60%).
1. Heritable or germline cases. In such cases first hit (mutation) occurs in one of the two alleles of retinoblastoma gene on the germ cells (gametes), before fertilization. This occurs in 40% of all cases either due to inheritence from the affected parent (10% cases) or sporadically in one of the gametes (30% cases). This means mutation will occur in all the somatic cells (predisposing to develop even nonocular tumours such as osteosarcoma). Second hit (mutation) occurs late in the postzygote phase and affects second allele of one or more retinal cells, resulting in multifocal and usually bilateral tumour formation. About 15% of heritable cases are unilateral. Some heritable cases have trilateral retinoblastoma (i.e., having associated pinealoblastoma). Heritable case can transmit the disease by autosomal dominant way to 50% of offsprings. However, due to variable penetrance only 40% are affected.
2. Non-heritable or somatic cases. About 60% of retinoblastoma cases occur sporadically by both hits (mutations) occurring in the same retinal cell in the embryo after fertilization. These mutations
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generally result in unifocal and unilateral tumours which cannot be passed on to the offsprings. Such patients are not predisposed for nonocular tumours.
Pathology
Origin.  Retinoblastoma arises as malignant proliferation of the immature retinal neural cells which are small round cells with large nuclei, i.e., it is a tumour of a group called small round blue cell tumour. Histopathology. The tumour chiefly consists of small round cells with large nuclei, resembling the cells of the nuclear layer of retina. These cells may present as a highly undifferentiated or well-differentiated tumour. Microscopic features of a well-differentiated tumour include Flexner-Wintersteiner rosettes, (highly specific of retinoblastoma), Homer-Wright rosettes, pseudorosettes and fleurettes formation (Fig. 12.34). Other histologic features are presence of areas of necrosis and calcification.
Clinical features
Common presenting features of retinoblastoma are listed in Table 12.2. These can be described stage-wise as below:
I. Intraocular stage of retinoblastoma
Presentation of this stage can be divided into two subgroups: quiescent presentations and painful red eye presentations.
a. Quiescent presentations include:
1. Leukocoria or yellowish-white pupillary reflex (also called as amaurotic cat’s eye appearance) is the commonest presenting feature (60%) (Fig. 12.35).



















Fig. 12.34 Histopathological picture of retinoblastoma

Table 12.2 Presenting features of retinoblastoma

Presenting features	Percentages Leucocoria	60% Strabismus	20%
Painful red eye	07% Poor vision	05% Asymptomatic	03% Orbital cellulitis	03% Unilateral mydriasis	02% Heterochormia iridis	01% Hyphema	01%














Fig. 12.35 Leukocoria right eye in a patient with retinoblastoma

2. Squint, usually convergent, is the second commonest mode of presentation.
3. Nystagmus is a rare feature, noticed in bilateral cases.
4. Defective vision. Very rarely, when the tumour arises late (3–5 years of age), the child may complain of defective vision.
5. Ophthalmoscopic features of the tumour. In the early stages, before the appearance of leukocoria, fundus examination after full mydriasis performed in children presenting with strabismus, poor vision, or other quiescent features may reveal the growth. Ophthalmoscopic signs in three types of retinoblastoma are as follows:
i.  Endophytic retinoblastoma (Fig. 12.36A): It grows inwards from the retina into the vitreous cavity. On ophthalmoscopic examination, the tumour looks like a well-circumscribed polypoidal mass of white or pearly pink colour (Fig. 12.36B). Fine blood vessels and sometimes a haemorrhage may be present on its surface. In the presence of
Chapter 12	Diseases of Retina	305














A	D













B	E











C	F
Fig. 12.36 Diagrammatic depiction (A&D); Fundus photographs (B&E); CT scan/MRI scan (C&F) of endophytic and exophytic retinoblastoma, respectively


calcification, it gives the typical ‘cottage cheese’ appearance. There may be multiple growths projecting into the vitreous.
ii. Exophytic retinoblastoma (Fig. 12.36D). It grows outwards and separates the retina from the choroid. On fundus examination it gives appearance of exudative retinal detachment (Fig. 12.36E, also see page 301).

iii.Diffuse infiltrating tumours show just a placoid thickness of retina and not a mass. Such cases are usually diagnosed late.
b. Painful red eye presentations.When retinoblastoma is left untreated during the quiescent stage, some patients may present with severe pain, redness, and watering. These symptoms occur either due to acute secondary glaucoma or apparent intraocular inflammation or orbital cellulitis.
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■Acute secondary glaucoma may occur either due to tumour pushing the lens-iris diaphragm forward or tumour cells clogging the trabecular meshwork. In this stage, eyeball is enlarged (buphthalmos) with apparent proptosis, conjunctiva is congested, cornea become hazy, intraocular pressure is raised. ■Apparent intraocular inflammation.Occasionally, picture simulating severe, acute uveitis usually associated with pseudohypopyon and/or hyphaema may be the presenting mode (retinoblastoma
masquerading as iridocyclitis).
■Orbital cellulitis like presentation occurs with necrotic tumours. It does not imply extraocular extension and the exact mechanism is not known.
Classifications of retinoblastoma
i. Reese-Ellsworth classification, which was of prognostic significance for the control of local disease has become irrelevant with the availability of newer chemotherapeutic agents and modes of therapy, and so not described here.
ii.International classification of retinoblastoma(ICRB), which is presently being followed worldwide to decide the treatment modality, is given below: Group A (very low risk): includes all small tumours <3 mm in greatest dimension, confined to retina, located >3 mm from fovea and >1.5 mm from the optic disc.
Group B (low risk): includes large tumours >3 mm in dimension, and any size tumours located <3 mm from fovea, and <1.5 mm from the optic disc margin.
Group C (moderate risk): includes retinoblastoma with focal seeds characterized by subretinal and or vitreous seeds ≤ 3 mm from the retinoblastoma. Group D (high risk): includes retinoblastoma with diffuse seeds characterized by subretinal and or vitreous >3 mm seeds from the retinoblastoma. Group E (very high risk):  includes extensive retinoblastoma characterized by any of the following: tumour touching the lens, neovascular glaucoma, tumour anterior to anterior vitreous face involving ciliary body and anterior segment, diffuse infiltrating tumour, opaque media with haemorrhage, tumour necrosis with aseptic orbital cellulitis, invasion of postlaminar optic nerve, choroid, sclera, orbit, and anterior chamber, or phthisis bulbi.
II. Stage of extraocular extension
Due to progressive enlargement of tumour, the globe bursts through the sclera, usually near the limbus or near the optic disc. It is followed by rapid fungation

and involvement of extraocular tissues resulting in marked proptosis (Fig. 12.37).
III. Stage of distant metastasis
It is characterised by the involvement of distant structures as follows:
1. Lymphatic spread first occurs in the preauricular and neighbouring lymph nodes.
2. Direct extension by continuity to the optic nerve and brain is common.
Differential diagnosis
1. Differential diagnosis of leukocoria. Various conditions other than retinoblastoma, which present as leukocoria are collectively called as ‘pseudoglioma’. A few common conditions are congenital cataract, inflammatory deposits in vitreous following a plastic cyclitis or choroiditis, coloboma of the choroid, the retrolental fibroplasia (retinopathy of prematurity), persistent hyperplastic primary vitreous, toxocara endophthalmitis and exudative retinopathy of Coats.
2. Endophytic retinoblastoma discovered on fundus examination should be differentiated from retinal tumours in tuberous sclerosis and neurofibromatosis, astrocytoma and a patch of exudative choroiditis. 3. Exophytic retinoblastoma should be differentiated from other causes of exudative retinal detachment in children such as: Coats’ disease (see pages 285 and 301).
Diagnosis
1. Examination under anaesthesia: It should be performed in all clinically suspected cases. It should include fundus examination of both eyes after full

















Fig. 12.37 Fungating retinoblastoma involving the orbit
Chapter 12	Diseases of Retina	307



mydriasis with atropine (direct as well as indirect ophthalmoscopy), measurement of intraocular pressure and corneal diameter.
2. Plain X-rays of orbit may show calcification which occurs in 75% cases of retinoblastoma.
3. Lactic dehydrogenase (LDH) level is raised in aqueous humour.
4. Ultrasonography and CT/MRI scanning are very useful in the diagnosis. CT/MRI also demonstrate extension to optic nerve, orbit and CNS, if any (Fig. 12.36C and F). However, CT should be used sparingly because of potential risk of radiation sarcomas.
Treatment
A.Conservativetumour destructive therapyto salvage eyeball is indicated when tumour is diagnosed at an early stage I, i.e., when tumour involves less than half of retina and optic nerve is not involved (usually in the second eye of bilateral cases). Present recommendations for the treatment are primary systemic chemotherapy (for chemoreduction) followed by focal therapy (for consolidation). Chemotherpy. Dose in mg/kg body weight for chemoreduction of retinoblastoma are as below: ■Standard dose CVE regimen, recommended for group A, B, and, C patients, consists of 3-weekly, 6 cycles of carboplatin (18.6 mg) on day 1, vincristine (0.05 mg) on day 1, and etoposide (5 mg) on day 1 and 2.
■High dose CVE regimen, recommended for group D patients, consists of 3 weekly, 6–12 cycles of carboplatin (28 mg) on day 1, vincristine (0.25 mg) on day 1 and etoposide (12 mg) on day 1 and 2. Focal therapy. Depending upon the location and size of the tumour, focal therapy can be chosen from the following modalities:
• Cryotherapy is indicated for a small tumour located anterior to equator.
• Laser photocoagulation is used for a small tumour located posterior to equator.
• Thermotherapy with diode laser is used for a small tumour located posterior to equator away from macula.
• Plaque radiotherapy is very effective against localised viterous disease and for the elevated tumours when laser is ineffective.
• External beam radiotherapy (EBR), once the mainstay of treatment, is now reserved for diffuse disease in the only remaining eye.
Note. If the above modalities are not available, the eyeball should be enucleated without hesitation.

B. Enucleation. It is the treatment of choice for group E tumors and when:
• Tumour involves more than half of the retina. • Optic nerve is involved.
• Glaucoma is present and anterior chamber is involved.
Eyeball should be enucleated along with maximum length of the optic nerve taking special care not to perforate the eyeball. If optic nerve shows invasion, postoperative treatment should include:
• External beam radiotherapy (5,000 rads) should be applied to the orbital apex.
• Chemotherapy,  consisting  of  vincristine, carboplatin, and etoposide which may be combined with cyclosporin should be supplemented.
C. Palliative therapy isgiven in following cases where prognosis for life is dismal in spite of aggressive treatment:
• Retinoblastoma with orbital extension,
• Retinoblastoma with intracranial extension, and • Retinoblastoma with distant metastasis.
Palliative therapy should include combination of: • Chemoradiation (CVE regimen),
• Surgical debulking of the orbit or orbital exentration, and
• External beam radiotherapy (EBRT)
Note. Exenteration of the orbit (a mutilating surgery commonly performed in the past) is now not preferred by many surgeons.
Prognosis
If untreated the prognosis is almost always bad and the patient invariably dies. Rarely spontaneous regression with resultant cure and shrinkage of the eyeball may occur due to necrosis followed by calcification; suggesting role of some immunological phenomenon.
If the eyeball is enucleated before the occurrence of extraocular extension, prognosis is fair (survival rate 70–85%).
Poor prognostic factors are: Optic nerve involvement, undifferentiated tumour cells and massive choroidal invasion.
ENUCLEATION
Enucleation refers to excision of the eyeball. It can be performed under local anaesthesia in adults and under general anaesthesia in children.
Indications
1. Absolute indications are retinoblastoma and malignant melanoma.
308	Section 3   Diseases of Eye



2. Relative indications are painful blind eye, non-responsive to conservative measure mutilating ocular injuries, anterior staphyloma and phthisis bulbi.
3. Indication for eye donation from cadaver is presently the most common indication for enucleation.
Surgical technique
1. Separation of conjunctiva and Tenon’s capsule (Fig. 12.38A): Conjunctiva is incised all around the limbus with the help of spring scissors. Undermining of the conjunctiva and Tenon’s capsule is done combinedly, all around up to the equator, using blunt-tipped curved scissors. This manoeuvre exposes the extraocular muscles.
2. Separation of extraocular muscles (Fig. 12.38B): The rectus muscles are pulled out one by one with the help of a muscle hook and a 3–0 silk suture is passed near the insertion of each muscle. The muscle is then cut with the help of tenotomy scissors leaving behind a small stump carrying the suture. The inferior and superior oblique muscles are hooked out and cut near the globe.
3. Cutting of optic nerve (Fig. 12.38C): The eyeball is prolapsed out by stretching and pushing down the eye speculum. The eyeball is pulled out with the help of sutures passed through the muscle stumps. The enucleation scissors is then introduced along the medial wall up to the posterior aspect of the eyeball.








A

Optic nerve is felt and then cut with the scissors while maintaining a constant pull on the eyeball.
4. Removal of eyeball. The eyeball is pulled out of the orbit by incising the remaining tissue adherent to it and haemostasis is achieved by packing the orbital cavity with a wet pack and pressing it back.
5. Inserting an orbital implant (Fig. 12.38D): Preferably an orbital implant (made up of PMMA Medpor or hydroxyapatite) of appropriate size should be inserted into the orbit and sutured with the rectus muscles. 6. Closure of conjunctiva and Tenon’s capsule is done separately. Tenon’s capsule is sutured horizontally with 6-0 vicryl or chromic catgut. Conjunctiva is sutured vertically so that conjunctival fornices are retained deep with 6–0 silk sutures (Fig. 12.38E) which are removed after 8–10 days. After completion
of surgery, antibiotic ointment is applied, lids are closed and dressing is done with firm pressure using sterile eye pads and a bandage.
Fitting of artificial prosthetic eye
Conformer may be used postoperatively so that the conjuctival fornices are retained deep. A proper sized prosthetic eye can be inserted for good cosmetic appearance (Fig. 12.39) after 6 weeks when healing of the enucleated socket is complete.