Subretinal Neovascular Membrane Research Articles

Overlay of conventional angiographic and en-face OCT images enhances their interpretation

BackgroundCombining characteristic morphological and functional information in one image increases pathophysiologic understanding as well as diagnostic accuracy in most clinical settings. En-face optical coherence tomography (OCT) provides a high resolution, transversal OCT image of the macular area combined with a confocal image of the same area (OCT C-scans). Creating an overlay image of a conventional angiographic image onto an OCT image, using the confocal part to facilitate transformation, combines structural and functional information of the retinal area of interest. This paper describes the construction of such overlay images and their aid in improving the interpretation of OCT C-scans.MethodsIn various patients, en-face OCT C-scans (made with a prototype OCT-Ophthalmoscope (OTI, Canada) in use at the Department of Ophthalmology (Academic Medical Centre, Amsterdam, The Netherlands)) and conventional fluorescein angiography (FA) were performed. ImagePro, with a custom made plug-in, was used to make an overlay-image. The confocal part of the OCT C-scan was used to spatially transform the FA image onto the OCT C-scan, using the vascular arcades as a reference. To facilitate visualization the transformed angiographic image and the OCT C-scan were combined in an RGB image.ResultsThe confocal part of the OCT C-scan could easily be fused with angiographic images. Overlay showed a direct correspondence between retinal thickening and FA leakage in Birdshot retinochoroiditis, localized the subretinal neovascular membrane and correlated anatomic and vascular leakage features in myopia, and showed the extent of retinal and pigment epithelial detachment in retinal angiomatous proliferation as FA leakage was subject to blocked fluorescence. The overlay mode provided additional insight not readily available in either mode alone.ConclusionCombining conventional angiographic images and en-face OCT C-scans assists in the interpretation of both imaging modalities. By combining the physiopathological information in the angiograms with the structural information in the OCT scan, zones of leakage can be correlated to structural changes in the retina or pigment epithelium. This strategy could be used in the evaluation and monitoring of patients with complex central macular pathology.

Ocular Conditions Associated with Peripapillary Subretinal Neovascularization, Their Relative Frequencies, and Associated Outcomes

To determine frequency and outcomes of conditions with peripapillary subretinal neovascular membranes (PSRNVMs). Retrospective observational case series. All patients from a private community-based retina practice diagnosed with a PSRNVM. Review of clinical charts, photographs, and fluorescein angiograms of 115 eyes of 96 patients, accrued over 18 years. Demographics, visual acuity (VA), laterality, neovascular membrane type and recurrence status over treatment course, and associated ocular conditions. Prevalences of reported associations were 52 (45.2%), age-related maculopathy (ARM); 45 (39.1%), idiopathic; 5 (4.3%), multifocal choroiditis; 3 (2.6%), angioid streaks; 2 (1.7%), histoplasmosis; 2 (1.7%), choroidal osteoma; 1 (0.9%), optic disc drusen; and 1 (0.9%), congenital disc anomaly. Newly recognized associations include pattern dystrophy (3 [2.6%]) and peripapillary pseudopodal pigment epithelial and choroidal atrophy (1 [0.9%]). Second-eye involvement was observed in 19.8% of patients over a median follow-up of 2 years. Median initial VAs were 20/40 for ARM-associated eyes and 20/30 for idiopathic eyes (P = 0.0230). Median final VAs were 20/70 for ARM-associated eyes and 20/32 for idiopathic eyes (P = 0.0261). The VA changes in the ARM-associated and idiopathic groups did not differ significantly (P = 0.1453). Recurrence of PSRNVMs after laser ablation was seen in 14 of 73 eyes (19.2%). A case of a PSRNVM as a cause of pseudopapilledema leading to unnecessary neurological imaging is reported. Close inspection of fellow eyes at the time of first eye diagnosis and regular follow-up afterward are indicated, given the high rate of eventual bilateral involvement regardless of associated condition. Laser ablation of PSRNVMs with broad treatment margins reduces recurrence rates relative to earlier series. The differential diagnosis of disc edema should include PSRNVMs. Pattern dystrophy can be associated with PSRNVMs.

Subretinal Neovascular Membranes Complicating Uveitis: Frequency, Treatments, and Visual Outcome

Purpose: Retrospective evaluation in a uveitic population of subretinal neovascular membranes (SRNMs), their occurrence, visual impact, and outcome in differently treated subgroups of patients. Methods: Medical records of patients were reviewed and cases with SRNM (n = 12) identified. Intraocular inflammation was classified according to vitreous examination records as high (2+ cells), low (1/2+ to 1+ cells), or inactive (0 cells). Visual outcome was considered to be +VA (same or gain of one or more Snellen lines) or −VA (loss of Snellen lines). In nine cases, treatment consisted of the oral administration of high doses of corticosteroids (CST) for one month, tapered down in favorable situations (+VA or SRNM angiographic regression) or maintained at half the dose in unfavorable situations (−VA or SRNM angiographic progression) while additional laser therapies, including photodynamic therapy (PDT), transpupillary thermotherapy (TTT), or argon laser therapy (CLT)), were performed in some of the cases. The above treatment scheme was not applied in three cases (pre-PDT period; undiagnosed underlying uveitis treated without CST). Results: Twelve out of 648 patients (1.9%) with uveitis developed SRNM. The mean visual impact was 4.5 Snellen lines and mean follow-up time was 19.5 months. Two patients with high intraocular inflammation had a favorable visual outcome with CST alone. Eight patients with low intraocular inflammation had a favorable visual outcome with CST alone in three cases, with additional laser therapy in four cases (PDT in 3 cases and TTT in 1 case), and exclusively with PDT in one case (undiagnosed uveitis). Two patients with no intraocular inflammation had unfavorable visual outcome with CST alone (no PDT/TTT available). Conclusion: SRNMs occurred as a rare complication of uveitis. Their visual outcome was relatively favorable. Although high doses of CST seem to be the first step in the management of SRNMs, alternative laser treatments should be considered early, especially in cases of absence or low intraocular inflammation.

Correlation Between Angiographic and Pathological Findings in Experimental Choroidal Neovascular Membranes After Transpupillary Thermotherapy

To evaluate the correlation between angiographic and pathological findings in experimental choroidal neovascular membranes after transpupillary thermotherapy (TTT). Experimental subretinal choroidal neovascular membranes were produced in the monkey eye macula by intense photocoagulation. TTT was delivered, targeting the choroidal neovascular membranes, using a diode laser at 810 nm. One week and 4 weeks after TTT, indocyanine green angiography (IA), fluorescein angiography (FA), optical coherence tomography (OCT), and histological examinations were performed. One week after TTT, indocyanine green dye leakage from choroidal neovascular membranes was reduced on IA, and FA showed staining in the late phase. Light microscopic examination showed numerous small-caliber blood vessels and persistent subretinal exudation. Four weeks after TTT, there was no indocyanine green dye leakage on IA, and FA showed staining. OCT showed a decrease in retinal detachment. Light microscopic examination showed fewer blood vessels and subretinal exudation had disappeared. Choroidal neovascular membranes were composed of fibrous tissue. Changes in angiographic and OCT findings observed after TTT were inferred to be the result of accelerated fibrosis due to TTT and the disappearance of exudation.

The Amsler chart is of doubtful value in retinal screening for early laser therapy of subretinal membranes. The West London Survey.

Validating the current protocol of Amsler chart grid surveillance for the early detection of subretinal neovascular membrane(SRN) in age-related macular degeneration(AMD), and investigating its value in facilitating early laser therapy. A retrospective pilot study. Central London eye hospital with dedicated 24-h ophthalmic casualty serving West and West-central London. 100 consecutive AMD patients who attended casualty with vision loss fulfilling the following criteria: patients had received and been instructed in the use of Amsler charts according to the unit's dispensation protocol,fluorescein angiography which confirmed new SRN. Patients presented over 20 months. Outcome measures were detection of SRN by the Amsler chart, and laser treatment of SRN. The Amsler chart surveillance protocol had detected SRN in 29 of the 100 patients. The surveillance protocol detected less than 30% of the specific patients who subsequently underwent laser treatment. A statistically significant difference was seen on comparing the ages of patients in whom the screening protocol was successful versus those in whom it was unsuccessful (student's t-test,P<3.2 x 103). Younger patients were more likely to be detected using the Amsler chart. A one-tailed Z2 test approached, but did not achieve, statistical significance (Z2 = 1.057,P <0.3) suggesting that patients who have already lost vision to SRN in one eye might not be more likely to be detected using the surveillance protocol than patients in whom SRN was affecting their first eye. In all, 38% of surveillance responders went on to receive laser therapy, compared with 37% of surveillance nonresponders. The current Amsler chart surveillance protocol is suboptimal for detecting SRN in AMD, and a proportion of cases suitable for early laser therapy may be missing rapid detection. The results are especially important since recent advances in laser therapy for SRN require early detection for optimal effectiveness.

Visual impairment caused by retinal abnormalities in mesangiocapillary (membranoproliferative) glomerulonephritis type II (“dense deposit disease”)

Patients with mesangiocapillary glomerulonephritis (MCGN) type II usually present by early adulthood with hematuria, proteinuria, and renal impairment, and these features often are accompanied by a partial lipodystrophy and an autoantibody for the alternative complement pathway convertase (C3NeF). The diagnosis of MCGN type II depends on the demonstration of “dense deposits” in the glomerular basement membrane (GBM). Most patients also have multiple subretinal white spots or drusen that are histopathologically identical with the GBM deposits and evident ophthalmoscopically by the time renal failure develops. Initially visual acuity and visual fields are preserved, but fluorescein angiography and specialized tests of retinal function, such as dark adaptation, electroretinography, and electrooculography, may be abnormal and will worsen progressively. Over the next 20 years, vision often deteriorates because of retinal atrophy, and sometimes because of subretinal neovascular membranes, macular detachment, and central serous retinopathy. The authors describe a patient with MCGN type II who presented with renal failure and impaired vision at the age of 59. He already had widespread retinal atrophy, and subsequently a subretinal membrane developed. The drusen seen in MCGN type II, like the partial lipodystrophy, are a helpful clinical pointer to the diagnosis of this condition. All patients with MCGN type II should be warned of the risk of retinal complications and reviewed by an ophthalmologist at presentation and regularly after about 10 years to minimize the loss of visual acuity from complications of the retinopathy.

An early-onset autosomal dominant macular dystrophy (MCDR3) resembling North Carolina macular dystrophy maps to chromosome 5.

To characterize the phenotype of an autosomal dominant macular dystrophy and identify the chromosomal locus. Thirteen members of a four-generation, nonconsanguineous British family were examined clinically and also underwent automated perimetry, fundus fluorescein angiography, and fundus autofluorescence imaging. After informed consent was obtained, blood samples were taken for DNA extraction, and genetic linkage analysis was performed. The retinal changes have an early age of onset and are confined to the macular region. The macular abnormalities vary from mild retinal pigment epithelium (RPE) pigmentary change to atrophy. Drusen-like deposits are present to various degrees and are characteristic of the phenotype. Subretinal neovascular membrane (SRNVM) is an established complication. Genetic linkage analysis established linkage to chromosome 5, region p13.1-p15.33 with a maximum LOD score of 3.61 at a recombination fraction of 0.00 for marker D5S630. The locus for this autosomal dominant macular dystrophy lies between flanking markers D5S1981 and D5S2031. A novel locus has been identified for early-onset autosomal dominant macular dystrophy on chromosome 5.

Massive vascular endothelium growth factor (VEGF) expression in Eales' disease

Eales' disease is an idiopathic retinal vasculitic and vaso-occlusive process complicated by extensive retinal neovascularisation and vitreous hemorrhages. The great propensity to produce retinal neovessels is one of the particular aspects of the disease that deserves to be further investigated. We report a case of Eales' disease having evolved over more than three decades, with a typical clinical presentation in one eye, while the other eye had to be enucleated because of a terminal neovascular glaucoma, thus allowing pathological examination. The functional right eye was treated by vitrectomy, cerclage, cryocoagulation and endolaser. The non-functional phthitic left eye was enucleated and submitted for histopathological and immunohistochemical examination using antibodies against vascular endothelial growth factor, T-cells, B-cells and Müller cells. Evolution was favourable in the operated right eye, following management of the inflammatory reaction. The histopathological examination of the left eye revealed an occlusion of the anterior chamber angle by rubeosis iridis, tractional retinal detachments, pre-, intra- and sub-retinal neovascular membranes, and vitrous hemorrhages. Diffuse positive anti-VEGF immunostaining was found at the level of the retinal neovascular membranes. The retina exhibited prominent Müller cell immunostaining, indicating extensive gliosis, and predominantly B cell infiltrates were found in the eye. The present study indicates a close relationship between the prominent neovascular proliferation in Eales' disease and the intense expression of VEGF. The increased expression of VEGF, when compared to other conditions inducing neovascularisation, might explain the severity of neovascular growth and the propensity of repeated vitrous hemorrhages in Eales' disease.

Transpupillary thermotherapy for occult subfoveal neovessels in age-related macular degeneration: importance of patient pigmentation for the determination of laser settings.

Presently the indication for transpupillary thermotherapy (TTT) is the treatment of retrofoveal occult subretinal neovascular membranes (OSRNM) for which PDT (photodynamic therapy) has a limited effect. The diode laser power settings given by the manufacturer (Iridex Co, Mountain View, California) have to be modulated according to several criteria including patient pigmentation. The purpose here was to report on a group of patients that presented chorioretinal atrophy after TTT. Thirty-eight eyes of 37 patients with OSRNM due to age-related macular degeneration underwent TTT. Indications to treat were diffuse exudative membranes, limited subfoveal OSRNM with a visual acuity of less than 0.4, or a drop of visual acuity of 3 Snellen lines or more since the previous examination. Dual fluorescein and indocyanine green angiography were used for angiographic follow-up. Treatment was performed according to the manufacturer's parameters. The group of patients that presented chorioretinal atrophy after TTT was analysed in this study Five patients presented a limited or spot-size related post-TTT chorioretinal atrophy. Pre-laser visual acuity was 0.34 +/- 0.13 and post-TTT visual acuity was 0.25 +/- 0.15. The OSRNM had disappeared in all cases. The common denominator in these patients was that they were white haired but upon questioning all happened to be dark-haired in their youth. Evolution towards atrophy can occur after TTT and probably depends on several factors. We showed that pigmentation is a parameter to be evaluated carefully before TTT and that laser power settings should progressively be diminished with increasing patient pigmentation. In white haired persons the original pigmentary status should be part of the patient history.

Photodynamic therapy of a subretinal neovascular membrane in type 2A idiopathic juxtafoveolar retinal telangiectasis

PURPOSE: To report the outcome of a patient with a subretinal neovascular membrane secondary to idiopathic juxtafoveolar retinal telangiectasis treated with photodynamic female therapy. METHODS: Interventional case report. A 43-year-old female with type 2A idiopathic juxtafoveolar retinal telangiectasis presented with a 2-week history of decreased vision and a subretinal neovascular membrane in the left eye. RESULTS: Visual improvement from 20/70-2 to 20/50-2 in the left eye was observed after two photodynamic therapy treatments of a juxtafoveal subretinal neovascular membrane with verteporfin, and was maintained through 7 months of follow-up. Fluorescein angiography showed no leakage specific to the subretinal neovascular membrane, but leakage from the juxtafoveal telangiectasis continued. CONCLUSION: A substantial improvement was seen in this patient after treatment of the juxtafoveal subretinal neovascular membrane by photodynamic therapy. Given the poor prognosis of these lesions, photodynamic therapy may therefore be a useful treatment for patients with subretinal neovascular membranes associated with idiopathic juxtafoveolar retinal telangiectasis.

Visual function after removal of subretinal neovascular membranes in patients with age-related macular degeneration.

Retinal pigment epithelial (RPE) cells have been transplanted to replace the RPE cells lost after surgical excision of choroidal neovascular membranes (CNV) associated with age-related macular degeneration. The purpose of this study was to analyze the visual function of eyes with altered RPE after surgical excision of choroidal neovascular membranes (CNV) associated with age-related macular degeneration, and to determine the effect of proliferated or migrated RPE cells on visual function. Forty-seven patients with age-related macular degeneration underwent excision of CNVs following vitrectomy and tamponade with sulfur hexafluoride (SF6) or silicone oil. The appearance of pre- or subretinal fibrosis and pigmentation of the lesion was considered to indicate proliferation and migration of RPE cells. Microperimetry was also performed. A significant correlation was found between the size of CNVs removed by surgery and the size estimated by indocyanine green angiography (P=0.0126). The mean number of RPE cells lost was estimated at 1.52 x 10(4). Pre- or subretinal fibrosis or pigmentation was observed in 37 patients (75.5%). The number of eyes with fibrosis was significantly higher in eyes with silicone oil tamponade than with SF6 tamponade (P=0.0016). A statistically significant correlation was not found between the presence of fibrosis or pigmentation and the postoperative visual acuity. Not all patients used the area of pigmentation for fixation, and microperimetry showed that some of the patients had scotomas in well-pigmented areas. Fibrosis and pigmentation after excision of CNVs may not always indicate normal function in these areas. These observations are especially relevant for transplantation of pigment epithelial cells in the future.

Role of fas-ligand in age-related maculopathy not established

PURPOSE: Fas-ligand expression on retinal pigment epithelium is hypothesized to have an inhibitory effect on human ocular neovascularization. METHODS: We studied Fas-ligand expression in the aging retinal pigment epithelium and in early and late stages of age-related maculopathy. Immunohistochemistry with antibodies against Fas-ligand was performed on paraffin-embedded sections of 23 human eye bank eyes (aged 45 to 96 years) and 12 eyes with exudative age-related maculopathy. RESULTS: Fas-ligand expression in retinal pigment epithelium was not related to age or to the presence of early age-related maculopathy. Furthermore, Fas-ligand expression in retinal pigment epithelium was similar in subretinal and subretinal pigment epithelium choroidal neovascular membranes. CONCLUSION: It appears to be unlikely that Fas-ligand expressed on retinal pigment epithelium controls the extension of choroidal neovascular membranes from subretinal pigment epithelium to subretinal.

Malattia leventinese presenting with subretinal neovascular membrane and hemorrhage

PURPOSE: To report a case of malattia leventinese involving subretinal hemorrhage. METHODS: Case report. RESULTS: Two weeks after initial presentation, the visual acuity of this 34-year-old man decreased to LE: 20/100. Funduscopic evaluation revealed a subretinal hemorrhage involving the center of the foveal in the left eye that was interpreted as secondary to a neovascular membrane on fluorescein angiography. The patient did well after the removal of the submacular material by pars plana vitrectomy. CONCLUSION: Patients with malattia leventinese may occasionally present with submacular hemorrhage. Prompt diagnosis and intervention may enhance the patient’s chance for visual improvement.

Functional assessment of the native retinal pigment epithelium after the surgical excision of subfoveal choroidal neovascular membranes type II: preliminary results.

Subretinal neovascular membranes (CNV) can occur in a variety of conditions. SRNVM most commonly occur in age-related macular degeneration (AMD), punctate inner choroidopathy (PIC)/multifocal inner choroidopathy (MIC) and myopia. AMD and CNV most common cause of blindness in western world.

Occurrence of atypical acute bilateral multifocal choroidal neovascularization in membranoproliferative glomerulonephritis type II

We report an unusual case of acute recurrent bilateral multifocal choroidal neovascularization that was associated with histologically proven membranoproliferative glomerulonephritis type II and did not resolve with laser photocoagulation. Early development of subretinal neovascular membranes with widespread retinal pigment epithelial changes in this condition may heraid poor prognosis despite laser ablation of the neovascular tuft.

Macular form of candidal chorioretinitis

Two patients had Candida albicans chorioretinitis secondary to systemic candidiasis, and each received medical treatment. The first patient's chorioretinitis was severe and long-standing. A large subfoveal membrane developed in 1 eye after the infection resolved. In the other patient, a unilateral subfoveal lesion developed after 9 days of infection. Both patients lost visual acuity to the level of counting fingers. The development of a subretinal neovascular membrane in the foveal area is a rare complication of C. albicans chorioretinitis. The anatomy of the submacular choroidal vasculature may explain this severe form of candidal chorioretinitis.

Complications of macular hole surgery.

Macular hole is a serious vision-threatening disease for which, until the early 1990s, no effective treatment was available. However, with advanced techniques in microsurgical vitrectomy surgery, effective and successful closure of macular holes now can be obtained. Many complications can occur after any ocular surgery. Some of the specific complications associated with macular hole surgery are RPE alterations, retinal detachments, CME, subretinal neovascular membrane, endophthalmitis, hypopyon, late re-opening of macular holes, increased intraocular pressure, visual field defects, and cataract formation. Because macular hole surgery is a relatively recent operation devised in the last 8 years, data on complications still are being compiled and studied to understand and minimize the rates of complications after such surgery. We hope that, in the future, the rate of complications after macular hole surgery will be no higher than that for any other ophthalmic procedure.

Use of a Macular Buckle in the Treatment of Exudative Age-related Macular Degeneration

To evaluate a macular buckle for exudative choroidal neovascularization secondary to age-related macular degeneration (ARMD). Forty-two eyes with choroidal neovascular membranes (CNVM) secondary to ARMD underwent surgical placement of a macular buckle. A Gore-Tex strip (2.0-2.5 mm wide) was button-holed through a 5 mm diameter silicone sponge (9 mm long) and placed behind the macula underneath the CNVM by the same surgeon (Dr Peyman) in all cases. Follow-up ranged from 7-76 months (mean, 20.9 months). Of 12 eyes with classic subfoveal CNVM: 4 (33%) gained 2 or more lines of Snellen visual acuity; 3 (25%) gained 1 line, remained the same, or lost 1 line; and 5 (42%) lost 2 or more lines (range + 6 to - 6 lines). Of 22 eyes with ill-defined subfoveal CNVM: 12 (54%) gained 1 line, remained the same, or lost 1 line; and 10 (46%) lost 2 or more lines (range + 1 to - 8 lines). Eight eyes with ill-defined juxtafoveal CNVM had the following visual acuity outcomes: 5 eyes (62%) maintained the same level of Snellen visual acuity (gained 1, 0, or lost 1 line); and 3 (38%) got worse (lost 2 or more lines of Snellen visual acuity, range + 1 to - 6 lines). Ten eyes (24%) bled subretinally during the follow-up period (average 11.5 months, range 14 days to 27 months), all outside the area of indentation of the macular buckle. The macular buckle treatment for exudative subretinal choroidal neovascular membranes in ARMD stabilized visual decline and displaced significant subfoveal hemorrhage.

Randomized trial of radiation for age-related macular degeneration

PURPOSE: To assess external beam radiation efficacy for subfoveal neovascularization associated with age-related macular degeneration. METHODS: All patients were evaluated in the same institution. In this prospective trial, 27 eyes (27 patients) with subfoveal neovascularization associated with age-related macular degeneration were randomized to either single fraction radiation (750 centigray) or observation. Endpoints were assessed by fluorescein angiography and Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity. Examiners were masked to patient treatment status. Parametric and nonparametric statistical analyses were performed. RESULTS: Twenty-seven patients were entered into the trial with a mean age of 76 years (range, 64 to 89) and a mean follow-up of 17 months (range, 7 to 32). The visual acuity loss was slightly less in the irradiated group, a finding of borderline significance ( P < .046). There was no significant difference in fluorescein angiographic evidence of subretinal neovascular membrane change in the control group vs the irradiated group. CONCLUSIONS: External beam radiation, at this dose and fractionation, did not appear harmful. There was slightly less visual loss in irradiated eyes. No difference in fluorescein angiographic characteristics of subfoveal neovascularization size or progression in eyes with age-related macular degeneration was noted.

Trends in vitreoretinal surgery at a tertiary referral centre: 1987 to 1996

AIMTo identify trends in vitreoretinal surgery at a tertiary referral centre from 1987 to 1996.METHODSA retrospective study of patients who had undergone vitreoretinal surgery at St Paul’s Eye Unit over...