- AGE RELATED MACULAR DEGENERATION - IJose M Ruiz Moreno, Javier A Montero, Francisco L Lugo (Spain)
- AGE RELATED MACULAR DEGENERATION - IIT Mark Johnson (USA)
- Dry AMD
- Exudative AMD
- AMD Variants
- Retinal Angiomatous Proliferation
- Polypoidal Choroidal Vasculopathy
Age Related Macular Degeneration — I
Jose M Ruiz Moreno, Javier A Montero, Francisco L Lugo (Spain)
INTRODUCTION
Age related macular degeneration (AMD) is a degenerative process involving the choriocapillaris, Bruch'smembrane, retinal pigment epithelium (RPE) and photoreceptors in the macula. AMD causes legal blindness in 1.7% of people aged 50 or older and is the leading cause of irreversible vision loss in developed countries in this group of age. AMD is classified as dry or atrophic and exudative or wet.
The prevalence of AMD increases with age from 40 years onwards. The prevalence of both forms among Caucasians is higher than among blacks.
CLINICAL SIGNS AND SYMPTOMS
Atrophic AMD is defined by the appearance of geographic areas of RPE atrophy greater than 175 microns in diameter which permits visualization of the choroidal vessels. Neovascular AMD is defined by RPE detachment associated to other signs of age related maculopathy, subretinal or sub RPE neovascularization, scars, glial tissue, fibrin, subretinal hemorrhages or hard exudates.
Hard drusen are white-yellowish deposits 50 microns in diameter with well defined contour that may appear in the posterior pole. Soft drusen are larger with poorly defined borders, tend to be confluent and appear in the perifoveal area and may cause drusenoid detachments. Pigment changes are hyper or hypo pigmented areas in the outer retina.
Atrophic AMD is a bilateral, slowly progressive condition, characterized by rapidly progressive loss of visual acuity and the appearance of a central or para central scotoma and metamorphopsia. Funduscopy reveals well defined atrophic areas larger than 175 microns with irregular borders. Choroidal vessels may be seen through the atrophic area. FA shows early, well defined hyperfluorescent areas without leakage.
Exudative AMD is characterized by rapidly progressive visual acuity loss with metamorphopsia and central scotoma caused by CNV in the posterior pole, frequently with a severe loss of visual acuity.
INVESTIGATIONS
Biomicroscopy and ophthalmoscopy reveal a grayish-yellowish, rounded or oval subretinal lesion which may be surrounded by a ring of pigment or blood.3
Figs 1A to J: (A and B) Hard drusen with atrophic phenomena. (C and D) soft drusen. (E and F) calcified drusen. (G and H) Drusenoid detachment. (I and J) Pigmentary changes (hyper and hypopigmentation)
Old lesions may show hard exudates or cystoid macular edema. New vessels frequently bleed causing subretinal hemorrhages. RPE detachments are frequent.
FA permits classification of CNV according to the distance to the fovea, the pattern or type of neovascularization and the components of the lesion. According to the distance to the fovea, CNV can be classified as extrafoveal 200 microns or more from the geometric center of the FAZ), juxtafoveal (1 to 199 microns) and subfoveal (affecting the geometric centre of the FAZ). According to the angiographic pattern, two types of CNV are differentiated: classic and occult. Classic CNV is characterized by a well delimited area of intense hyperfluorescence in the early frames with leakage in the intermediate frames which may hide the borders of the CNV. Pathologically they are between the RPE and the neurosensory retina. Early frames show irregular hyperfluorescence, mottled or with irregular elevations of the RPE. Late frames show fluorescein leakage which accumulates in the RPE detachment. RPE may be well or ill defined, and fluorescence is less intense than in classic forms or can be mottled and non homogeneous. These findings originate two FA patterns characteristic of occult CNV: fibrovascular pigment epithelium detachment (FVPED) and late leakage of Undetermined Source (LLUS).
FVPED are characterized by an irregular elevation of the RPE with mottled hyperfluorescence 1 to 2 minutes after fluorescein injection, well or ill defined and with leakage in the late frames. LLUS are characterized by fluorescein leakage in the late frames; the origin can not be determined and is different from classic and FVDEP.
Other components should be considered, such as blood, blocked fluorescence and serous PED.
According to the proportion of lesion occupied by the different components, three main types of lesions can be considered: Predominantly Classic CNV (classic CNV > 50% of entire lesion), Minimally classic CNV (classic CNV < 50%, > 0% area of entire lesion) and Occult with no classic CNV.
OCT reveals soft drusen as elevated RPE with no posterior shadowing towards the choroid whereas PED appears as RPE elevation with shadowing. CNV appears as a hyperreflective band anterior to RPE inducing posterior shadowing. The presence of fluid may be a sign of activity of CNV. Fibrosis appears as a hyperreflective band with no fluid accumulation. Occult lesions present diffuse or cystic intraretinal fluid and PED. OCT provides important information about the persistence of active CNV and the healing process, revealing the presence of RPE rips or changes and elevation of RPE. Presently, the follow up of CNV associated with AMD is performed basically by OCT.
Research is focused on the complement gene which might be responsible for 43% of the cases. Many other genetic studies will be required to confirm the causality of AMD related to this gene.5
Figs 2A to F: (A) Fundus eye of a patient with atrophic ARMD. (B to E) Fundus eye (right and left) and fluorescein angiography (FA) of a patient with atrophic ARMD in both eyes. (F) OCT of the right eye with thin retina
Oxidative stress causes damage to the RPE and the choriocapillaris. RPE lesions trigger an inflammatory response in Bruch'smembrane and choroid stimulating the production of an abnormal extracellular matrix which further modifies the behavior of RPE increasing the damage to the retina and the choroid.
Pharmacological inhibition of angiogenesis is the new therapeutic modality to treat CNV in AMD. New possibilities of blocking angiogenesis are under research, such as blocking the expression of the genes after DNA transcription (RNA interference).
RNA interference is a cellular mechanism that silences the expression of one protein in a specific a powerful way using short RNA molecules addressed against a specific RNAm. Other therapeutic approach under research is the blockade of cellular receptors for VEGF tirosinkinase 2 and VEGF trap. VEGF trap-eye is a recombinant protein consisting of human VEGF receptor extracellular domains fused to the Fc portion of human immunoglobulin IgG1. VEGF trap is a specific blocker that binds and inactivates circulating VEGF in the blood stream and in the extracellular extravascular space.
DIFFERENTIAL DIAGNOSIS
Differential diagnosis should be established with Polypoidal Choroidal Vasculopathy (PCV) and Retinal Angiomatous Proliferation (RAP).
TREATMENT
Thermal laser has been much restricted presently. The results of the MPS group at 5 years revealed recurrences at 5 years in 41% of the cases, with a marked visual acuity loss in 52% of the treated eyes. Only in cases with well defined extrafoveal CNV distant enough from the fovea to permit treating the whole lesion without damaging the FAZ. Transpupillary thermotherapy has been abandoned.
Verteporfin PDT is known to reduce the patient's perception of scotoma. The appearance of recurrences and the need to retreat is still high. Combined treatment with intravitreal triamcinolone acetonide (TA) and PDT unite the short-term effect of PDT inducing CNV closure with the anti-inflammatory effects of intravitreal TA. Combined treatment PDT and intravitreal antiangiogenic drugs is being tested.
Antiangiogenic drugs: Positive results have been reported with intravitreal injections of an anti VEGF aptamer (Macugen®) to treat wet AMD. A fragment of a humanized monoclonal antibody anti VEGF (ranibizumab, Lucentis®) has been reported to be effective as well as the off label use of the complete antibody (bevacizumab, Avastin®).7
Figs 3A to C: Fundus eye, FA (late phase) and OCT of a patient with predominantly classic subfoveal CNV associated to ARMD
Macugen® (sodium pegaptanib) is a pegylated aptamer with anti VEGF properties and a molecular weight of 50 KD which acts specifically and with high affinity on the isoform 165 of VEGF, which is the most frequent in retinal CNV. The drug is injected intravitreally every six weeks. 0,3 mg Macugen® was useful vs sham injections to avoid 3 lines loss (70% versus 55%; P < 0,001). Regarding safety, and after analyzing adverse events related to the drug and the injecting procedure revealed that Macugen® was well tolerated at all concentrations.
Lucentis® inhibits VEGF mediated neovascularization. A molecular weight of 48 kD (smaller than the complete monoclonal antibody, 149 kD) facilitates its penetration into the subretinal space.
The pivotal masked randomized controlled phase III trials with Lucentis® (MARINA and ANCHOR) revealed that treated patients gained an average 6.6 and 5.4 letters with 0.5 and 0.3 mg respectively, vs an average loss of 14.9 letters in the control group after 2 years; ANCHOR presented 11.3 and 8.5 letters gain respectively vs an average loss of 9.5 letters in the PDT group. More than 90% of the treated patients maintained BCVA after 2 years vs 60% in the controls. A new trial was designed (PIER) to reduce the number of injections treating the eyes with 3 injections during the first 3 months, and once every 3 months thereafter. However visual outcome was worse than in MARINA and ANCHOR.
Avastin® is a humanized monoclonal antibody antiVEGF that links to all the biologically active forms of VEGF as occurs with Lucentis® Bevacizumab was approved by the FDA for the intravenous treatment of metastatic colorectal cancer. Bevacizumab was initially used systemically to treat exudative AMD and was later injected intravitreally. BCVA improves one week after the injection and is maintained for 3 months. Mean retinal thickness is significantly decreased at 3 months follow-up.
It is not clinically feasible to perform intravitreal injections every four weeks for 2 years. The most accepted injecting schedule presently derives from the PRONTO trial: 3 monthly injections with a re injection criteria including increased central retinal thickness > 100 microns, BCVA loss > 5 letters with retinal fluid in OCT, new classic CNV or hemorrhage and persistence of fluid 1 month after the injection. Its results were similar to those of MARINA and ANCHOR with a lower number of injections (average 5.5/year, mean time after the first re-injection 4.3 months).
We have to inform about the advantages, drawbacks, risks and legal situation of each drug. The cardiovascular risk of these patients should be individually considered.9
Figs 4A to F: (A to C) Fundus eye and FA (early and late phase) of a patient with predominantly classic subfoveal CNV associated to ARMD. (D to F) fundus eye and FA (early and late phase) of a same patient after three PDT treatments
PROGNOSIS
The natural history of CNV is a fibrous disc shaped scar known as disciform. The presently available therapies may modulate new vessels growth and hyperpermeability, reducing the formation of disciform scars and improving visual outcome. However, we are still not able to modify the atrophic and degenerative changes in RPE and choriocapillaris.
Figs 5A to I: (A to C) Fundus eye and FA (early and late phase) of a patient with minimally classic subfoveal CNV associated to ARMD. (D to F) fundus eye and FA (early and late phase) of a same patient three months after one PDT treatment combined with high dose intravitreal triamcinolone. (G to I) fundus eye and FA (early and late phase) of a same patient six months after one PDT treatment combined with high dose intravitreal triamcinolone
Figs 6A to F: (A to C) Fundus eye and FA (early and late phase) of a patient with occult subfoveal CNV associated to ARMD (late leakage of undetermined source). (D to F) fundus eye and FA (early and late phase) of a same patient after one PDT treatment combined with high dose intravitreal triamcinolone
Figs 7A to F: (A to C) Fundus eye and FA (early and late phase) of a patient with occult subfoveal CNV associated to ARMD (fibrovascular PED). (D to F) fundus eye and FA (early and late phase) of a same patient after four PDT treatments with persistent activity of the CNV
Figs 8A to C: Fundus eye and FA (early and late phase) of a patient with occult subfoveal CNV associated to ARMD (late leakage of undetermined source)
Figs 9A to C: Fundus eye and FA (early and late phase) of a patient with occult subfoveal CNV associated to ARMD (fibrovascular and serous PED)
Figs 10A to I: (A to D) Red free fundus eye and FA (early, middle and late phase) of a patient with polypoidal vasculopathy. (E and F) ICG (early and middle phase) showing small hyperfluorescent polyps. (G to I) Fundus eye and FA (early and late phase) of a same patient after treatment by argon green laser photocoagulation
Figs 11A to I: (A to D) Fundus eye and FA (early, middle and late phase) of a patient with Retinal Angiomatous Proliferation stage II (RAP). (E and F) ICG (early and middle phase) showing intraretinal angiomatous proliferation. (G to I) fundus eye and FA (early and late phase) of a same patient after treatment by of a same patient six months after one PDT treatment combined with high dose intravitreal triamcinolone
Figs 12A to H: (A to C) Fundus eye and FA (early and late phase) of a patient with predominantly classic subfoveal CNV associated to ARMD. (D to F) red free fundus eye and FA (early and late phase) of a same patient after argon green laser photocoagulation with new CNV re-growth in the edge of a previous scar. (G and H) fundus eye and FA (early and late phase) of the same patient after second argon laser treatment with no activity of the CNV
Figs 13A to H: (A to D) Fundus eye and FA (early, middle and late phase) of a patient with occult subfoveal CNV associated to ARMD. (E and F) horizontal and vertical OCT previous treatment. (G and H) OCT of a same patient after one Lucentis® intravitreal injection
Figs 14A to J: (A to C) Fundus eye and FA (early and late phase) of a patient with occult subfoveal CNV associated to ARMD. (D and E) horizontal and vertical OCT previous treatment. F: OCT of a same patient after one Lucentis® intravitreal injection. (G to I) fundus eye and FA (early and late phase) of a same patient after three intravitreal injections of Lucentis® (J) Final OCT after treatment
Figs 15A to J: (A to C) Fundus eye and FA (early and late phase) of a patient with minimally classic subfoveal CNV associated to ARMD. (D to G) OCT study during treatment with four Macugen® intravitreal injections. (H to J) FA (early and late phase) and OCT after treatment
Figs 16A to J: (A to C) Fundus eye and FA (early and late phase) of a patient with occult subfoveal CNV associated to ARMD. (D) horizontal OCT previous treatment. (E and F) OCT study during treatment with three Avastin® intravitreal injections. (G to J) Fundus eye, FA (early and late phase) and OCT of a same patient after three intravitreal injections of Avastin®
Figs 17A to G: (A to D) Fundus eye and FA (early, middle and late phase) of a patient with occult subfoveal CNV associated to ARMD. (E and F) Horizontal and vertical OCT previous treatment. (G) fundus photography of the same patient showing retinal pigmentary epithelium tear after one Lucentis® intravitreal injection
Age Related Macular Degeneration — II
T Mark Johnson (USA)
DRY AMD
INTRODUCTION
Prevalence
- Represents 80% of cases of AMD
- Increased prevalence with age
- 6% of patients > 52 years
- 20% > 75 years.
Risk Factors
- Family history
- Precise genetics of AMD remain unclear
- Y402H variant of complement factor H gene may account for significant amount of the risk of macular degeneration
- Light racial pigmentation
- Smoking
- Hypertension
- Cardiovascular disease.
CLINICAL SIGNS AND SYMPTOMS
Symptoms
- Asymptomatic
- Decreased vision
- Decreased contrast acuity
- Distortion.
Signs
- Drusen
- Yellow subretinal deposits
- Hard drusen: well defined yellow deposits
- Soft drusen: ill defined deposits
- Coalescence produces drusenoid RPE detachment
- Pigmentary hypertrophy
- Geographic atrophy
- Well defined of the RPE and choriocapillaris leaving areas of visible deep choroids and sclera.
INVESTIGATIONS
Fluorescein Angiography
Indications
- Rule out evidence of CNVM.
Results
- Soft drusen have pooling of dye under the drusen resulting in late hyperfluorescence without leakage
- Areas of atrophy show well defined choroidal staining.
Macular Perimetry
Indications
- Evaluation of macular function.
Results
- Demonstrates significant macular dysfunction in dry AMD
- May be used to locate eccentric fixation points for visual rehabilitation.
DIFFERENTIAL DIAGNOSIS
- Congenital
- Stargardt disease
- Best disease
- Central areolar choroidal atrophy.
- Acquired
- Myopic degeneration
- Drugs (example chloroquine)
- Trauma
- Posterior uveitis.
TREATMENT
Antioxidant Therapy
Indications
- Extensive intermediate (63-124 microns) drusen
- At least 1 large druse (>124 microns)
- Non central geographic atrophy
- CVNM in fellow eye.
Methods
- Supplementation with high dose beta carotene, vitamin C, vitamin E and zinc
- Smokers should receive zinc supplementation alone due to concerns about related lung cancers.
Results
- Age Related Eye Disease Study demonstrated a significant reduction in the risk of development of advanced macular degeneration
- Odds Ratio for developing advanced AMD in patients treated with antioxidants plus zinc 0.72 (0.52-0.98)
Laser
- Macular laser has been observed to reduce the number of drusen evident in the macula
- Initial clinical trials observed a reduction in drusen with a marginal visual benefit but possible increased risk of development of CNVM
- Currently considered investigational.
Inferences
- Dry AMD is the most common form of AMD
- 5 year incidence of development of CNV in patients with bilateral drusen is approximately 13%.
BIBLIOGRAPHY
- AREDS Group. A randomized, placebo controlled clinical trial of high dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and visual loss. Arch Ophth. 2001:119; 1417–36.
- Leibowitz HM, et al. The Framingham Eye Study Monograph VI. Surv Ophth. 1980:24(suppl); 428–57.
- Smiddy WE et al. Prognosis of patients with bilateral macular drusen. Ophth. 1984:91; 271–77.
- The Choroidal Neovascularization Prevention Trial Research Group. Laser treatment in eyes with large drusen. Short term effects seen in a pilot randomized clinical trial. Ophth. 1998: 105;11–23.
EXUDATIVE AMD
INTRODUCTION
Prevalence
- 10% of macular degeneration
- Accounts for majority of legal blindness secondary to AMD
- 80% of legal blindness secondary to AMD is due to exudative AMD
- Prevalence of legal blindness in Caucasian population secondary to exudative AMD is 2.7/1000 persons.
Incidence
- 5 year incidence of CNVM in patients with bilateral drusen is about 13%
- 3 year incidence of CNVM in patients with unilateral CNVM is about 30%.
Risk Factors
- Family history
- Smoking
- Cardiovascular disease
- Hypertension.
CLINICAL SIGNS AND SYMPTOMS
Symptoms
- Decreased visual acuity
- Distortion.
Signs
- Subretinal fluid: Appears as turbid, grey elevation of retina
- Subretinal hemorrhage
- Lipid exudation: Typically at margins of extend of exudation
- Serous pigment epithelial detachment: Dome shaped elevation of RPE, may have a notch at the margin of the choroidal neovascular membrane
- Fibrovascular pigment epithelial detachment: irregular elevation of RPE, may have associated fibrosis
- Subretinal fibrosis: Fibrotic tissue indicative of regressed choroidal neovascularization.
Fig. 4: Recurrent subfoveal CNVM at the margin of prior MPS laser treatment. Subretinal blood and fluid are present
INVESTIGATIONS
Fluorescein Angiography
Describes the pattern of the choroidal neovascularization.
Location
- Subfoveal: Located under the center of the fovea
- Juxtafoveal: 1-199 mm from fovea
- Extrafoveal: Greater than 200 mm from fovea.
Pattern of CNVM
- Classic: Well-defined early hyperfluorescence with late leakage
- Occult: Ill-defined early hyperfluorescence with late leakage or ill defined late leakage with an obvious early source.
ICG Angiography
Allows visualization of CNV through areas of blood, subretinal fluid or pigment epithelial detachment.
Plaque
Greater than 1 disc area of hyperfluorescence that is less intense than a hot spot.
Hot Spot
Bright hyperfluorescent lesion < 1 disc area, typically indicative of RAP lesion or polypoidal CNV (see below).
High Speed ICG Angiography
Utilize rapid capture of the early perfusion of the retina, phi motion produces a continuous motion of early vascular flow allowing visualization of arterial and venous flow of the CNVM.
OCT
Visualize intraretinal edema, subretinal fluid and PED.
DIFFERENTIAL DIAGNOSIS
- Myopic choroidal neovascularization
- Choroidal rupture
- Angioid streaks
- Idiopathic
- Presumed ocular histoplasmosis.
Figs 5A and B: Early and late fluorescein angiogram of patient with a well-defined choroidal neovascular membrane with late leakage
TREATMENT
Focal Laser.
Indications
- Extrafoveal CNVM
- Juxtafoveal: The scotoma generated by focal laser has led most practitioners to use alternative treatments
- ? Subfoveal CNVM.
Methods
- Confluent ablation of the entire CNV complex with treatment border of 100 microns beyond the CNV margin.
Results
- Treatment reduces the risk of severe visual loss (< 20/200)
- Treatment is associated with permanent scotoma
- While subfoveal MPS trial showed better stabilization of vision with treatment the scotoma and immediate visual decline has led to alternative therapies
- Recurrence rates are high
- Extrafoveal MPS had a 54% 5 year recurrence rate with the majority of recurrences extending into the fovea
- Recurrence is associated with a greater risk of visual loss.
Photodynamic Therapy
Indications
- Subfoveal choroidal neovascularization
- Juxtafoveal choroidal neovascularization.
Methods
- Intravenous infusion of verteporfin dye
- Administer 6 mg/m2
- Application of 689 nm laser to lesion at 50 J/cm2
- Treatment is extended 300-500 microns beyond the border of the lesion.
Results
- PDT slows the rate of visual loss with exudative AMD
- CNVM with > 50% classic component may experience a greater benefit from treatment with PDT
Transpupillary Thermotherapy
Indications
- Subfoveal choroidal neovascularization.
Methods
- 810 nm diode laser applied to the entire choroidal neovascular membrane to obtain light grey burn to the entire neovascular complex.
Results
- Initial case series demonstrated promising results
- Randomized controlled trial failed to show significant benefit for TTT in patients with AMD.
Intravitreal Anti VEGF Therapy
Indications
- Monotherapy for choroidal neovascularization
- ? Role in combination therapy.
Methods
- Available Agents
- Pegaptanib (Macugen)
- Ranibizumab (Lucentis)
- Bevacizumab (Avastin)
- Method of Administration
- intravitreal injection
- frequency of dosing varies with medication type.
- Complications
- Endophthalmitis
- Cataract
- Retinal detachment
- Uveitis.
Results
- Clinical trials demonstrate pegaptanib is effective at preventing visual loss
- Clinical trials have demonstrated pegaptanib to be better than placebo at stabilizing visual loss
- Repeated injections are required every 6 weeks
- Limited subset of patients regains visual acuity.
Fig. 7B: Same patient 2 weeks post photodynamic therapy with complete closure of neovascular complex
Figs 8A and B: Patient with choroidal neovascularization prior to therapy with occult leakage, pigment epithelial detachment and retinal edema. Visual acuity 20/125
- Clincal trials demonstrate benefit to ranibizumab therapy
- MARINA Trial studied ranibizumab versus placebo in occult CNVM
- 95% of treated eyes lost < 15 ETDRS letters
- 25-34% gained > 15 ETDRS letters
- ANCHOR Trial demonstrated ranibizumab to be superior to verteporfin for treatment of predominately classic CNVM
- Case series report significant success with intravitreal bevacizumab therapy
- Direct trial comparing ranibizumab and bevacizumab is pending.
Intravitreal Steroids
Indications
- Monotherapy for occult CNVM
- Combination therapy with PDT, feeder vessel treatment.
Method
- Intravitreal injection.
Results
- Cases series describing combined use of triamcinolone with PDT suggest a prolonged treatment effect and possibly improved visual outcomes
- Use of triamcinolone as monotherapy is not well supported by published studies.
Submacular Surgery
Indications
- Unclear at present time
- ? Subfoveal CNVM in elderly patient without significant drusen.
Method
- Vitrectomy with removal of the subfoveal CNVM.
Result
- Submacular Surgery Trial did not show significant benefit to surgery compared with observation at 2 year follow up.
Macular Translocation
Indication
- Unclear at this time.
Methods
- 360 degree translocation
- Vitrectomy followed by cutting the retina 360 degrees allowing a large degree of macular translocation
- Secondary extraocular muscle surgery is required due to torsional diplopia
- Limited translocation
- Vitrectomy with creation of localized macular detachment
- Scleral imbrication allows small degree of macular translocation.
Result
- Case series described benefit in selected patients however no RCT has been conducted to date.
Inferences
- Poor untreated natural history
- Early recognition and treatment can lead to preservation of vision.
BIBLIOGRAPHY
- Gragoudas ES, Adamis AP, Cunningham ET, et al. Pegaptanib for neovascular age-related macular degeneration. New Engl J Med. 2004;351: 2805–16.
- Guyer DR, Yannuzzi LA et al. Classification of choroidal neovascularization by digital indocyanine green video angiography. Ophth 1996; 103: 2054–60.
- Hawkins BS, et al. Surgery for subfoveal choroidal neovascularization in age-related macular degeneration: Ohthalmic findings. SST report no.11. Ophthalmology 2004: 111; 1967–80.
- Macular Photocoagulation Study. Argon laser photocoagulation for neovascular maculopathy: 3 year results. Arch Ophth 1986; 104: 694–701.
- Macular Photocoagulation Study. Krypton laser photocoagulation for neovascular lesions of age related macular degeneration. Arch Ophth 1990; 108; 816–24.
- Macular Photocoagulation Study. Laser photocoagulation of subfoveal neovascular lesions in age related macular degeneration. Arch Ophth 1991; 109: 1220–31.
- Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age related macular degeneration. New Engl J Med. 2006: 355; 1419–31.
AMD VARIANTS
RETINAL ANGIOMATOUS PROLIFERATION
INTRODUCTION
- Variant of AMD believed to originate with intraretinal neovascularization rather than subretinal
- May account for up to 15% of wet AMD
- Female > Male
- Elderly.
Classification
- Stage I: neovascularization confined to the neurosensory retina
- Stage II: neovascularization extending from the retina into the subretinal space
- Stage III: neovascularization extending from the retina into the choroid.
CLINICAL SIGNS AND SYMPTOMS
- Symptoms of wet AMD
- Intraretinal hemorrhage (versus subretinal hemorrhage)
- Cystic intraretinal edema
- Pigment epithelial detachement
- Later development of subretinal neovascularization with retinal – choroidal anastamoses.
INVESTIGATIONS
Fluorescein Angiography
- Majority have occult CNVM.
ICG Angiography
- Focal Hot Spot: Intraretinal neovascularization
- Plaque: Associated subretinal neovascularization.
High Speed ICG
- Demonstrates the intraretinal and subretinal components of neovascularization.
OCT
- Intraretinal cystic edema
- Intraretinal neovascularization may be demonstrated in some cases.
Fig. 9A: Color photo of patient with RAP lesion. Note the predominant intraretinal hemorrhage rather than subretinal hemorrhage
Fig. 9B: Fluorescein angiogram demonstrating occult leakage inferonasally with cystoid macularedema. Small flecks of intraretinal hemorrhage block fluorescence. Clinical features are typical for a RAP lesion. Geographic atrophy is noted superiorly
Fig. 9C: Single frame from high speed ICG angiogram demonstrates small focus of intraretinal neovascularization (RAP)
TREATMENT
Methods
- Focal Laser
- Photodynamic Therapy
- Anti VEGF injections.
Result
- To date no large trials have been conducted comparing treatment modalities.
INFERENCES
- Common variant form of wet AMD characterized by intraretinal neovascularization
- Natural history is poor
- High rate of bilateral disease
- Unclear what the optimal treatment modality is currently.
BIBLIOGRAPHY
- Gross NE, et al. Nature and risk of neovascularization in the fellow eye of patients with unilateral retinal angiomatous proliferation. Retina 2005; 25: 713–18.
POLYPOIDAL CHOROIDAL VASCULOPATHY
INTRODUCTION
- Middle aged female
- More common in pigmented racial groups
- Association with hypertension.
CLINICAL SIGNS AND SYMPTOMS
- Large subretinal or sub RPE hemorrhages
- Lesions center on optic nerve rather than fovea.
INVESTIGATIONS
Fluorescein Angiography
- Mainly occult CNV.
ICG Angiography
- Focal Hot Spots in grape like clusters.
High Speed ICG
- Central feeder vessel supplying dilated vascular clusters.
Fig. 10A: Fluorescein angiogram shows subretinal hemorrhage and ill-defined leakage of dye superior to the optic nerve. Window defects consistent with macular drusen are present centrally
MANAGEMENT
Treatment Options
- Focal Laser
- Feeder Vessel Laser
- Photodynamic Therapy
- Anti VEGF therapy.
Result
- No comparative trials of therapy for polypoidal CNVM exist.
Inferences
- Variant of AMD with hemorrhage centered on optic nerve rather than fovea
- More common in non
- Caucasian populations
- Unclear natural history
- No comparative trials for therapy.
BIBLIOGRAPHY
- Kleiner RC, Brucker AJ, Johnston RL. Posterior uveal bleeding syndrome. Ophth 1984; 91(suppl 9): 110.
- Otani A, Sasahara M, Yodoi Y, et al. Indocyanine green angiography: guided photodynamic therapy for polypoidal choroidal vasculopathy. Am J Ophthalmol 2007; 144; 7–14.