Age-Related Macular Degeneration (AMD): The Continuum of Normal Aging and Disease

Degenerative Changes
 RPE and Bruch’s membrane disturbances

Formation of drusen

These changes are commonly observed in the eyes of most elderly persons to some degree

Cell death and functional loss

Only in some individuals do these age related changes progress to this stage

Transition from normal aging to disease (with a loss of functional vision)

Drusen are players in retinal disease, RPE disease, and AMD

Drusen occurs in 70% of all eyes over the age of 50 yrs

Drusen are signs of RPE abnormality/ atrophy

Precursor/ participant in AMD

Peripheral/ posterior pole location

RPE cells deposit collagenous basement membrane into Bruch's (drusen):

Mucopolysaccharides and lipids.

Cause unknown (choriocapillaris dysfunction?)

Solar exposure

Photodynamic effects can lead to superoxide free radical formation, which promotes drusen/ lipofuscin formation. Lipofuscin and drusen are thought to be
RPE phagocytized photoreceptor outer segments that are driven by a solar induced mechanism.

Increased deposition of drusen is associated with RPE thinning and atrophy

Choriocapillaris breakdown results in hypoxia (and release of VEGF), RPE atrophy, and drusen formation

Pathophysiology and implications of drusen are not fully understood- Drusen do alter Bruch's membrane and can lead to choroidal neovascularization

Hard drusen

Typically seen in dry AMD

Soft drusen

Amorphous material between inner and outer layers of Bruch's membrane

Large, ill-defined, confluent

More inclined to lead to exudative (wet) AMD

Allows formation of choroidal neovascular membrane (CNVM)

As RPE atrophy increases, the risk of wet AMD decreases. RPE atrophy represents poor choroidal perfusion and hypoxia- neo can not be supported due to choriocapillaris dropout.
However, vision still suffers.
Age Related Macular Degeneration (AMD): Risk Factors

Typical age: 75-85 years

Framingham population-based prevalence study criteria: 20/30 or worse
1

Prevalence:
52-64 yrs 1.6%
65-74 yrs 11%
75 yrs + 27.9%

Family hx

Maternal or sibling history strongest

Hand grip weakness

Alcohol consumption

Cardiovascular disease

Hypertension

Hyperlipidemia

Hyperopia

Aphakia

Short stature

Lightly pigmented hair/ eyes

Caucasian

Wet form more common in Caucasian patients

Smoking (esp. men)

Heavy smoking more than doubles risk

Nutritional

Decreased vit B,E zinc, magnesium intake

Higher incidence with alcohol consumption: poor diet

However, moderate intake of wine and carotenoids (leafy greens) may help

Leutein may be most protective

Drusen (as discussed above)

Wet: soft drusen

Dry: hard drusen
Dry (Atrophic or Non-exudative) AMD

80% of AMD cases

Macular drusen is a risk factor for both wet and dry AMD

Soft drusen – typically wet AMD

Hard drusen – typically dry AMD

Depigmentation

Granular clumping of RPE/RPE hyperplasia

Macular RPE atrophy

Mottled, "moth eaten" appearance of retina/RPE

Coalesce into geographic atrophic areas of RPE and choroid

200-5000 microns (1/7DD-3DD)

Bilateral, symmetrical

10% will progress to wet AMD
2

Clinical Pearl: Dry AMD is not diagnosed by a single finding, but instead constitutes a spectrum of findings involving drusen, RPE atrophy, functional vision loss and/or RPE pigment changes. The beginning of the spectrum constitutes normal aging changes and the end represents severe vision loss.
Dry AMD: Geographic Atrophy

Progressive loss of RPE and choriocapillaris

Macrophages replace drusen with fibrous tissue or dystrophic calcification

Once this occurs, CNVM will no longer form

Loss of photoreceptor function

Non-viable capillaries: neo will not form in non-viable, atrophic zones

20% risk of CNVM at edge of lesion

Loss of retinal layers

VA 20/25 - 20/400 (approx)
Dry AMD: Management

Photodocument

Home amsler

UV protection

Anti-oxidant vitamins with zinc supplements (Results of the Age-Related Eye Disease Study
(AREDS): Archives of Ophthalmology October 2001, JAMA October 2001)

For those taking high-potency antioxidants and zinc combined formula, there was a decrease (vs placebo) in the percent of patients who progressed to advanced AMD at
5 years

Visual acuity loss

Only the high-potency antioxidants (vitamin C, vitamin E, beta carotene) and zinc combined formula statistically significantly reduced the odds of visual acuity loss

Neovascularization

The combined high-potency antioxidants and zinc product statistically significantly reduced the odds of developing choroidal neovascularization

Conclusions: Those with extensive intermediate sized drusen, at least one large drusen, or non-central geographic atrophy in one or both eyes or those with advanced AMD or vision loss due to AMD in one eye and without contraindications such as smoking, should consider taking a supplement of antioxidants plus zinc

F/u q3mos-q6mos

Low vision consult

90% of dry AMD pts are not legally blind
Wet (Exudative) AMD: Choroidal Neovascularization

8-20% of cases of AMD are wet (actually, up to 12% may be unknown, according to
Framingham study)

Presence of exudate, hemorrhages, or suspected gray-green lesion as this implies that choroidal neovascularization and wet AMD has formed. However, hemorrhage or exudation may obscure part or all of CNVM
3


Choroidal Neovascularization

Bruch's disruption
 Diffuse thickening of Bruch’s with soft drusen which predisposes to breaks in
Bruch’s membrane

Presence of VEGF enhances development
 Other diseases can cause Bruch’s disruption

RPE/ Bruch's breaks

Diffuse thickening with soft drusen predisposes Bruch’s membrane to breaks

Soft drusen often precursor, but not always

Chronic Inflammation Theory
 Higher number of lymphocytes, macrophages, fibroblasts found in Bruch’s membranes of patients with AMD
 Inflammation causes breaks in Bruch’s membrane?

Implication are not yet understood

Choroidal neovascular membrane (CNVM) infiltrates from choriocapillaris

Under the RPE and sensory retina

RPE detachment with turbid fluid or blood may represent CNVM

Round/oval gray-green elevation
 Don’t look only for gray-green appearance. Look for fluid and blood.

Associated findings:

Lipid exudate

Blood

Sensory RD

Classic CNVM

Well defined membrane on angiogram

About 10% of cases

Occult CNVM

About 90% of cases

Ill defined membrane on angiogram

CNVM may be subfoveal, juxtafoveal (1-199 microns from center of macula), or extrafoveal (> 200 microns from center of macula

FA and possibly indocyanine green (ICG) imaging: hot spots with late spread of hyperfluorescence.

Must get FA within 72 hrs because membranes can grow 10 microns/day;
Suspected/actual CNVM is an ocular urgency

ICG may be indicated to better visualize outline of membrane

ICG dye absorbs and emits fluorescence in the near IR spectrum

Better able to penetrate hemorrhage, melanin, fluid

Better for occult CNVM detection

Hypoxia and VEGF

RPE tear

Serous RPE detachments

Hemorrhagic RPE/sensory retinal detachments

10% risk of wet AMD in 4.3 yrs if pt. has bilateral macular drusen
4


90% of pts. who are legally blind from AMD have wet AMD

VA 20/200-20/800
Clinical Pearl: Sub-retinal hemorrhages are identified by your ability to see distinct retinal vessels overlying the hemorrhaging area. If you can see the retinal vessels, then the hemorrhage must be beneath the retina.
Clinical Pearl: Soft drusen are more inclined to lead to wet AMD
Wet (Exudative) AMD: Disciform Scarring:

Fibrovascular material following CNVM development

Most cases of CNVM progress to this stage

Replaces most of sensory retina, RPE

May continue to grow and invade new areas

Results in death of tissue and severe visual loss

Yellow-brown-black (RPE hyperplasia)

Surgical excision may modestly improve vision
Wet AMD: Management

Laser photocoagulation

Photodynamic therapy (PDT)

Intravitreal steroid injection

Anti-angiogenic factors

UV protection

Anti-oxidant vitamin therapy

Macular drusen - home amsler

Low vision consult
Wet AMD: Laser Treatment

50% of wet AMD cases are potentially laser treatable with subsequent reduction in vision loss (i.e., the CNVM is juxta-or extrafoveal)

Of those pts. (the 50%) that are treatable:

75% of wet AMD pts pass through this "treatable" stage

80% are treatable within 2 weeks

Only 50% are treatable in 4 weeks

Only 20% are treatable in 8 weeks

Krypton laser for juxtafoveal net (less likely to be absorbed by RPE)

Specificity for choroidal layers
 Recurrence rate: 47% of tx’ed eyes

Argon Study: argon laser for extrafoveal net (>200 microns from center of FAZ)

Treat with argon blue-green laser

Laser energy absorbed by RPE and choroidal pigment and turned into heat and dissipated into adjacent tissues. CNVM are closed by coagulative necrosis

Xanthophyll pigment absorbs green argon laser and transmits heat to adjacent structures, thus cannot be used juxtafoveally.
5


Recurrence rate after treatment- 53%

There is no good treatment for a subretinal/ subfoveal hemorrhage. Some surgeons will inject a gas bubble into the eye and place the patient face down in order to tamponade the hemorrhage and spread the blood out.

There is no great treatment for a subfoveal CNVM. Some surgeons are lasering subfoveal membranes in the thought that the laser damage will be less severe than the natural course of the disease.

Short-term results are significantly reduced vision. However, long-term results support treating sub-foveal CNVM as these patients do better. However, patients can often retain good vision with a subfoveal CNVM for an indeterminate period of time. Laser reduces vision immediately. This treatment should only be done after vision has dropped to
20/200
Wet AMD: Photodynamic Therapy (PDT)

Patient receives IV infusion of a light activated drug that collects in the tissues of the macula.
Low powered laser (664 nm) activates the drug, which forms singlet oxygen. This induces platelet aggregation and thus CNVM thrombosis. This is chemical obliteration of CNVM without damaging overlying retina and RPE. Damages unhealthy tissue but does not disturb healthy adjacent or overlying tissues.
 Difficulty: Indicated only for subfoveal membrane whose areas is at least 50% ‘classic’
CNVM. Only about 10% of CNVM are ‘classic’.

Another problem: PDT causes up-regulation of VEGF which increases leakage and propensity to form neovascularization

Verteporfin: Visudyne

High rate of side effects

Highly photosensitizing. Must absolutely avoid the sun for 3 days

High degree of skin necrosis needing skin grafts if dye extravasates during injection

Can not have subretinal fibrosis

Leakage is reduced, but not stopped

70-80% leak again in 1 year; however, doesn’t bleed, scar, or atrophy
Clinical Pearl: Photodynamic therapy is a well-accepted therapy for wet AMD, though the stand-alone results are not great. Likely, it will be used in conjunction with other therapies for best results.
Wet AMD: Intravitreal Steroid Injection:

Stabilizes vascular membranes and reduces vascular permeability.

Endophthalmitis is most significant complication
Clinical Pearl: Intravitreal injections of steroids are being investigated and used for edema secondary to vascular occlusions, diabetes, cystoid macular lesions, and wet age related macular degeneration. This promises to be a significant advancement in the treatment of maculopathies secondary to edema.
6

Macugen (pegaptanib sodium)

Oligonucleotide with high affinity for VEGF, preventing its uptake by endothelial receptors

Intravitreal injection q 6 weeks

Approved, but has not fared well and is not commonly used as other chemicals have performed better

Stand-alone therapy

87.5% of eyes had stabilized or improved vision after 3 months

25% of eyes improved three or more lines

Macugen + PDT

60% of eyes improved three or more lines at 3 months
Lucentis (ranibizumab)

Recombinant anti-VEGF antibody fragment that binds to VEGF

Intravitreal injection q 4 weeks

Approved and more successful than Macugen

94% of eyes with stable or improved vision at 98 days

On average, two lines of vision gained

26% of eyes improved three or more lines at 98 days

Studies comparing monthly Lucentis injections vs. quarterly PDT are being done
Avastin

Anti-colon cancer drug; accidentally found when patients with wet AMD patients undergoing chemotherapy reported improved vision

Not approved for this use (intravitreal injection for AMD), but very popular and economical
Clinical Pearl; Despite all of the new developments in wet AMD management, if a patient develops subfoveal CNVM today, he or she is pretty unlucky.
Other Conditions Associated with Choroidal Neovascular Membrane Formation:

Degenerative conditions

Wet AMD (#1 cause)

Degenerative myopia (#3 cause)

Angioid streaks

ONH drusen

Idiopathic Central Serous Chorioretinopathy (ICSC) and RPE detachment

Inflammatory and infectious conditions

Ocular Histoplasmosis syndrome (#4 cause)

Toxoplasmosis

Tuberculosis

Sarcoidosis

Syphilis

Rubella
7


Choroidopathies (serpiginous, birdshot, punctate inner)
 Beçhet’s syndrome

Vogt-Koyanagi-Harada syndrome (VKH)

Hereditary
 Best’s disease

Dominant drusen

Fundus flavimaculatis

Choroideremia

Retinitis pigmentosa (RP)

Tumors

Malignant melanoma

Choroidal hemangioma

Metastatic tumors

Trauma

Excessive PRP

Choroidal rupture

Miscellaneous

Idiopathic CNVM (#2 cause)

Radiation retinopathy

Retinal detachment

Tilted disc syndrome
Choroidal Rupture

Result of direct injury to globe

Hemorrhages present if recent

May involve macula

Vision loss occurs here only if RPE is damaged

Vision and field loss variable

Generally, retina overlying rupture is normal

5 yr possibility of CNVM
Idiopathic Central Serous Chorioretinopathy (ICSC)

Also known as central serous chorioretinopathy (CSC) and central serous retinopathy (CSR)

Serous retinal or pigment epithelial detachments in macular area

Loss of foveal reflex

Transient and potentially recurrent

Recurrence rate is 20-30%

Breakdown of RPE cells allowing seepage to occur into sensory retina

Typically, a focal conduit through RPE into sensory retina

Theorized to occur secondary to vasomotor instability or sympathetic nervous excitation

Predisposing conditions such as drusen are absent

RPE detachment can commonly occur simultaneously

RPE separates from Bruch's; retina separates from RPE

Due to RPE disruption, there may be associated RPE hyperplasia
8


Male: female 10:1

20-50 yrs (mid 30's). This should not be diagnosed in a patient over age 55 yrs

Must look for CNVM in older pts.

Type A personality

Caucasian

FA appearance: smokestack with 1 or 2 well demarcated cavities.

Sensory RD is diffuse

RPE detachment is well demarcated

Presents with decreased VA, metamorphopsia, hyperopic shift

Highly associated with steroid use (of all kinds)
Clinical Pearl: It is an error to diagnose ICSC in a patient over the age of 55 years. In these cases, consider the cause to be CNVM until proven otherwise.
Idiopathic Central Serous Chorioretinopathy: Management

Home amsler and observation

Discontinue all steroids

Excellent prognosis

60% recover 20/20

1-6 mos course

Self-limiting

RPE decompensation may complicate matters. "sick RPE syndrome"

Focal dysfunction of RPE resulting in slow, chronic oozing through RPE

Retina and RPE remain flat

Poor prognosis

Decreased VA with RPE changes

Possible CNVM formation

Direct photocoagulation to leaking areas in severe or non-remitting cases

Krypton better than argon: less recurrences

Laser treatment only considered after 3-4 mos of non-resolution (6 mos. Better)

Turbid fluid

Non-clearing

Intolerable sx to pt.

Sick RPE

Recurrence in eyes with visual field defect from previous episode

Previous event in other eye left permanent defect

Leakage must be outside of FAZ

Treatment does not affect rate of recurrence or final acuity; it only hastens the process

Laser may aggravate pre-existing choroidal neovascular membrane or ICSC. This is ‘like putting fertilizer on a weed’.
Clinical Pearl: Despite all of the advancement in treating wet maculopathies with intravitreal steroid injections, ICSC must never be treated with this modality. Severe vision loss has occurred.
9

Retinal Pigment Epithelial Detachment:

Occur as idiopathic alterations in Bruch's membrane allows fluid to seep under RPE

Can occur as result of choroidal neovascularization

Usually occurs as some dysfunction of RPE, e.g. drusen

Serous RPE detachment: ophthalmoscopic appearance:

Oval/round, small, well demarcated dome-shaped elevation.

Clear fluid

If no CNVM- observe

Hemorrhagic RPE detachment: ophthalmoscopic appearance

Blood confined to sub-RPE space, dark red, elevated

Blood usually indicates CNVM

Occasionally, blood dissects through RPE and gives hemorrhagic RD and may even break through retina to give vitreous hemorrhage

90% of cases have concurrent sensory retinal detachment (ICSC) as well

On FA, the domed lesion fluoresces early and evenly and maintains well defined borders late into angiogram

Up to 30% of patients over 55 yrs who develop RPE detachments will have CNVM

CNVM can cause RPE detachment

RPE tears occur in 10% of cases

Permanent vision loss can result from RPE atrophy, RPE tear, or CNVM
Clinical Pearl: RPE detachment tends to be small and well localized and fills early on FA, but does not spread.
Clinical Pearl: RPE and CSC typically occur simultaneously.
Idiopathic Juxtafoveal Retinal Telangiectasia (IJRT)
 A similar condition to Coat’s disease and may be a variation

A cause of macular edema and reduced acuity

A developmental anomaly with subsequent leakage

Two forms: unilateral and bilateral

Unilateral

Occurs only in men

Asymptomatic until after age 40

1-2 DD area often temporal to fovea

Vision reduced, but not usually below 20/40

Similar to macroaneurysm, but too close to fovea

Bilateral

Occurs in either sex

Usually 40-60 years

Symmetrical

Less than 1 DD area

Vision typically 20/30 or better

Both may present with intraretinal edema and retinal hemorrhages
10


Hard exudates and RPE hyperplastic abnormalities

This condition is greatly under-diagnosed

Always consider this condition in patients presenting with idiopathic parafoveal edema or dot/blot hemorrhages especially if there is no history of ischemic vascular disease
Idiopathic Juxtafoveal Retinal Telangiectasia: Management

Conservatism

Photocoagulation with grid argon green or krypton red if there is progressive loss of vision

Intravitreal injection of Avastin/ steroids

PDT

Consider testing for HTN and DM in patients with parafoveal hemorrhaging. If these diseases are not present, then telangiectasia is the likely cause.

There is no strong relationship between this condition and any systemic disease
Clinical Pearl: Always consider idiopathic juxtafoveal retinal telangiectasia in cases of mild paramacular hemorrhaging. Too often, this condition is overlooked and the findings are ascribed to diabetic retinopathy (even if the patient doesn’t have diabetes!)
Cystoid Macular Edema (CME)

Not a disease , but a finding

Special arrangement of nerve fibers in Henle's layer allows for CME

Honeycomb appearance. Initial fluid accumulation is within Muller cells, which gets into extracellular spaces causing cystoid spaces in OPL. Occurs almost always from leaking perifoveal capillaries

Cystic edema: difficult to perceive ophthalmoscopically

Petalloid appearance on FA; cystic appearance on OCT

If cause is inflammatory, there may also be disc edema

Often (erroneously) termed Irvine-Gass syndrome

CME s/p cataract extraction (ICCE complicated by vitreous loss))

60% detectable by FA

10% symptomatic

Peak incidence is 6-10 weeks after surgery

> 75% resolve spontaneously within 6 months

Causes:

Vitreous traction during surgery

Inflammation

Light toxicity from operating microscope causing free radical release leading to prostaglandin synthesis with subsequent vasodilation and vasopermeability of perifoveal capillaries

Also occurs secondary to:

Vaso-occlusive disease (vascular occlusion, DM)

ICSC

Pars planitis

Uveitis (posterior or anterior)
11


Arterial disease

Retinitis pigmentosa

Nd:YAG capsulotomy

Ocular surgery

Cataract (Irvine Gass syndrome)

RD surgery

Vitrectomy

Glaucoma surgery

Cryo, laser

Radiation retinopathy

Choroidal tumors

AMD

Epiretinal membrane

PVD

Vitreous loss

Use of epinephrine in aphakes

Anecdotal evidence of Xalatan causing CME

CME is caused by many factors. Diagnosis is by clinical suspicion and confirmed by FA.
CME can be very subtle. Acuity may be 20/20.

Pt. may present with decrease VA and/or metamorphopsia or may be asymptomatic
Cystoid Macular Edema: Management

Post-cataract extraction- prognosis is good:

50% spontaneously recover in 6 mos; 20% may have it in excess of 5 yrs.

Topical steroids QID

Topical NSAIDS (Voltaren) QID

Oral NSAIDS

Diamox

Oral and depot steroids

Vitrectomy and/or grid photocoagulation

Now being commonly treated with intravitreal steroid injections

Long term CME can lead to foveal cyst formation which, after rupturing, results in a macular hole
Clinical Pearl: CME is frequently asymptomatic and best appreciated on a fluorescein angiogram.
Clinical Pearl: While CME after cataract extraction is often called Irvine-Gass syndrome, be aware that this term specifically refers to CME following complicated intracapsular cataract extraction.
Macular Holes

Anything disturbing the macula can cause a hole

CME is a strong precursor due to foveal cyst formation
12


Foveal cyst is a strong precursor

There is a weak vitreoretinal adhesion at the macula

Proliferation of Muller cells may be responsible for the traction development

PVD can cause macular irritation and cyst formation

Vitreomacular traction (VMT) syndrome

Patients may have a perifoveal PVD with traction remaining on the center of the fovea

The disturbance to the architecture of the retina can range from macular edema to a localized retinal detachment

This leads to cyst formation

Opening of the cyst creates the hole

Cyst can rupture and result in hole formation

PVD can operculate macula (rare)

Macular holes can be lamellar (20/80 acuity) or full thickness (20/200 acuity)

6-22% bilaterality

New theories contend that tangential forces from contraction of the posterior cortical vitreous cause idiopathic spontaneous macular holes
Stages of Macular Hole Formation

Stage 1: foveal cyst from CME or disruption to vitreoretinal interface. May form lamellar hole. Mild acuity loss and metamorphopsia. Only 50% progress from here.

Lamellar holes are partial thickness and appear slightly reddish. Depressed foveal area w/o FLR. 20/80 acuity. Late hyperfluorescence on FA.

Stage 2: lamellar hole more likely to occur. Retinal tear possible. 70% progress from here.

Stage 3: Full thickness macular hole. Poor prognosis for vision central acuity.

Stage 4: Full thickness macular hole with poster vitreous separation

Full thickness holes: defined edges, round, very red due to transmission from choroid.
Early hyperfluorescence on FA. Maintenance of Bruch's membrane.
Macular Holes: Risk for Fellow Eye

Stage 1: 50% stability

PVD in fellow eye w/o cyst: very low risk

No PVD in fellow eye: 28-44% risk for fellow eye due to remaining vitreoretinal adhesion

RPE defects in fellow eye: 80% risk
Macular Holes: Treatment

Vitrectomy may relieve VMT

Vitrectomy to relieve traction in Stage 1 is very helpful. Vision may improve and F/T hole may be aborted

Vitrectomy in Stage 2 leads to vision stabilization

At this stage. The most effective surgical treatment for full thickness macular holes involves vitrectomy to remove traction at the hole edge and either gas or silicone oil tamponade. Here, the expanding bubble flattens out the edges of the hole and the recontact with the RPE seems to stimulate fibroblastic activity with a filling in of the hole. Not perfect, but vision does restore very well. Techniques are constantly changing. Works best if hole present for less than 1 year.
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Solar Retinopathy

Associated with:

Solar eclipse observation

Religious rituals

Drug (illicit) use

Sunbathing

The false belief that it is therapeutic

Psychosis

Stupidity

Sun gazing- photo-oxidative damage :

Solar retinopathy occurs likely from a combination of photochemical and thermal mechanisms.

Retinal cells die by apoptosis in response to light-induced injury and the process of cell death is perpetuated by diverse, damaging mechanisms.

Two classes of photochemical damage have been recognized.

The first type is characterized by the rhodopsin action spectrum, and is thought to be mediated by visual pigments, with the primary lesions located in the photoreceptors.

The high energy wavelengths and low levels of ultraviolet A (UV-A) radiation are absorbed by the outer retinal layers with subsequent photochemical damage, likely involving oxidative events.

The second type of damage is generally confined to the retinal pigment epithelium
(RPE). The RPE pigmentation absorbs sunlight energy, converting it to heat with a resultant rise in temperature, resulting in a burning of the RPE.
This RPE damage is often permanent.

Positive after images

Metamorphopsia

Acuity 20/30-20/100 (hours later)

May be edematous immediately afterwards

After several days, will have reddish spot with pigment halo, which progresses to red lamellar foveal depression

Cystic changes may develop

May simulate hole or progress to hole

Acuity may improve over 6 mos, but visual deficits will remain Reports regarding spontaneous visual recovery vary greatly.

Improvement in visual acuity occurs mostly during the first 2 weeks to 1 month after the incident; Further improvement in visual acuity is not observed after 18-months

There is no treatment for stupidity
Clinical Pearl: Small, symmetrical foveal cysts should be investigated for a history of sun gazing.
Preretinal Membrane

Also known as cellophane maculopathy, epiretinal membrane, preretinal gliosis, surface wrinkling, proliferative vitreoretinopathy, macular pucker
14


Caused by break in ILM with retinal glial cells proliferating on surface

Occurs from VMT

Wrinkled cellophane appearance

Metamorphopsia, macular edema, vision loss, or asymptomatic

Often benign and self-limiting

Macular pucker in 3-5% of cases due to vitreous shrinkage following laser, cryotherapy, RD surgical procedures: proliferative vitreoretinopathy

May be idiopathic

Only 5% have < 20/200 acuity

Treatment: vitrectomy with membrane peeling

Vision < 20/70
 Typically has a rapidly advancing course initially, then stabilizes and doesn’t change.
Choroidal Folds:

Do not mistake this for epiretinal membrane

Can occur secondary to hypotony and congenitally short eyes

Horizontal folding of choroid, often across macula

Vision may be somewhat diminished or distorted

This is strongly indicative of a retro-orbital tumor or other mass lesion

Acquired hyperopia

These patients need orbital imaging
Clinical Pearl: Carefully examine every case of suspected epiretinal membrane to ensure that the patient actually does not have choroidal folds from a tumor. Choroidal folds are horizontal whereas epiretinal membrane often radiates from the macula. If in doubt, seek consult or order orbital imaging.
Degenerative Myopia

Also known as pathological myopia

Myopic stretching of photoreceptors, posterior pole and disc area

True alteration of globe structures

Ethnic predilection for Chinese, Japanese, Arabian descent

Common in fetal alcohol syndrome, Downs syndrome, albinism

Refractive error not conclusive

Globe elongation

Posterior staphyloma: leads to legal blindness

Choroidal and choriocapillaris atrophy

Lacquer cracks: breaks in Bruch’s membrane. Conduit for CNVM

Similar to angioid streaks, but do not always connect with the disc or radiate

Fuch's spots: RPE hyperplasia overlying CNVM

First sign of CNVM formation

Pathognomonic for CNVM in degenerative myopia

May cause sub-retinal hemorrhaging from rubbing the eye

CNVM generally is not treated because it generally does not grow significantly and often
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spontaneously involutes. Also, laser scar expands as the eye elongates
Angioid Streaks

Breaks in Bruch's membrane

Occur as a result of connective tissue diseases or disease that cause abnormal deposition of metallic salts in Bruch’s membrane, causing it to become fragile

Elastic fibers stretch, causing a thinning of the RPE allowing the choroid to be visualized

May be peripapillary or radial

Appear frighteningly similar to blood vessels

50% have associated systemic disease

Pseudoxanthoma elasticum (80-90%) - PXE

Inherited AR disease

Loss of skin resiliency with the appearance of papules in intertriginous areas (e.g.,
Axilla, behind knee, on neck)

Combination of angioid streaks and PXE is known as Groinblad-Stanberg syndrome

Vascular changes are most problematic: pts can have arterial damage that ranges from absent peripheral pulse to pain on exertion to severe hemorrhaging when the vessels rupture (bleeding in GI tract, nose, uterus, intracranially)

Ehlers-Danlos syndrome (8-15%)

Sickle cell disease (1-2%)

Others:
 Marfan’s syndrome

Senile elastosis
 Paget’s disease

Epilepsy

Acromegaly

Pituitary tumors

Risk of dry AMD

14% risk of CNVM- difficult to treat as Bruch's membrane is further compromised by the treatment. Do not do prophylactic treatment.

Associated buried drusen of ONH- may cause additional peripheral vision loss

May be asymptomatic or may present with disciform scarring

Polycarbonate lenses- avoid trauma

Medical w/u to r/o systemic disease
Retinal Arterial Macroaneurysm (RAM):

Isolated dilated area of a major retinal (arterial) branch

Isolated ballooning of the vessel wall

Can happen rarely within the venous system (retinal venous macroaneurysm)

Within the radius of the third branching

Usually unilateral, but may be multifocal

Associated with hypertension, arteriolosclerosis, retinal emboli, cardiovascular disease

Results from focal damage to vessel wall

Edema, hemorrhage, exudation often present
16


Hemorrhage at various levels

Occurs in yrs 50-80, mostly females

25% show high rate of mortality at 5yrs

Threat to vision if macula involved

Once bleeding occurs, the macroaneurysm often becomes sclerosed

FA results: fills in the arterial phase with late stage leakage
Retinal Macroaneurysm: Management

Medical evaluation for systemic risk factors

Asymptomatic cases (without hemorrhage or exudation) not threatening the macula- monitor q6mos (use of home monitoring as well)

Localized hemorrhage and exudation not threatening the macula- monitor q1-3mos

Photocoagulation if the macula is threatened or edematous, or if there is not spontaneous selfsealing after 3 months of observable bleeding

Photocoagulation is recommended if there is pulsation to the aneurysm wall

Venous macroaneurysms may develop in areas of BRVO, HRVO, CRVO
Clinical Pearl: Retinal macroaneurysm should be considered in cases of extensive localized retinal hemorrhaging. This condition can mimic BRVO and is often found in association with BRVO.
Clinical Pearl: Retinal macroaneurysm can cause subretinal, intraretinal, pre-retinal, and vitreous hemorrhage. Think of RAM whenever you see a patient that has multi-layer hemorrhages.
Hyperviscosity Syndromes:

Increased blood viscosity

Abnormally high accumulation of blood components

Reduced O
2
carrying capacity of blood

Hypoxia

Dilated (tortuous or non-tortuous) veins

Venous beading

Also see: CWS, edema, hemorrhages

Other findings:

Conjunctival vascular sludging

Crystalline deposits in bulbar conjunctiva and corneal stroma

Pars plana cysts

Choroidal effusion

Bilateral retinopathy of venous dilation and peripheral hemorrhages

Retinal findings may be absent in patients with extremely high viscosity and may be present in patients with other hematological changes such as anemia

May cause retinal vascular occlusions

Tends to resemble bilateral CRVO

Causes:
17


Polycythemia (excess RBC's)

Increased platelets

Increased plasma proteins with myeloma

Massive leukocytosis in leukemia

Cryoglobulinemia

Waldenstrom's macroglobinemia is the most common cause of hyperviscosity

Myeloma in which large quantities of IgM (plasma protein) are produced

Weight loss, malaise, hepatosplenomegaly, bleeding tendencies

Management involves addressing underlying disease
Anemia:

Deep and superficial hemorrhages

CWS

Pale fundus

Disc edema possible

Normal retinal vessels
 Roth’s spots

Superficial hemorrhage with white, infarcted center

Similar to both diabetic and hypertensive retinopathy, except that there are no exudates as in diabetic retinopathy and there is no attenuation of the vessels as in HTN retinopathy

Treatment is the management of the underlying anemia
Clinical Pearl: Abnormally dilated retinal veins are an indication for you to pursue blood evaluation on your patient.
Systemic Lupus Erythematosus

Microvascular ischemia from vasculitis

Choroidal infarcts may occur

Bullous subretinal fluid may occur

Common changes include: CWS (without HTN), hemorrhages, Roth's spots
Clinical Pearl: A large number of CWS (without other retinopathy) should lead you to consider SLE.
Drug Toxicity: Chloriquine and Hydroxychloriquine

Anti-malarial drugs: used to treat collagen-vascular disease (SLE) and arthritis.

Chloroquine, hydroxychloroquine (Plaquenil): bull's eye maculopathy- Heavy macular pigmentation surrounding by depigmented area surrounded by pigmented area. Loss of acuity, night vision, color perception. Irreversible changes. Maximum safe dosage for chloroquine is 250mg QD. Maximum safe dosage for Plaquenil is 400 mg QD. Also causes reversible corneal stromal opacification. Manage with DFE q6mos and photos and threshold visual fields (central 10-2). It usually takes 2-3 yrs to occur.

Risk increase:
18


Duration, dose, low body weight, renal disease, increased age
Drug Toxicity: Tamoxifen

Nolvadex

Treatment of breast cancer

Binds with estrogen receptors

Punctate white macular deposits

Looks like drusen or talc retinopathy

Reversible
19