Bullous Variant of Central Serous Chorioretinopathy: Expansion of Phenotypic Features Using Multimethod Imaging.

PURPOSE: To define the phenotypic characteristics of the bullous variant of central serous chorioretinopathy (CSC) using multimethod imaging. DESIGN: Retrospective, observational case series. PARTICIPANTS: Twenty-one eyes of 14 patients with bullous retinal detachment resulting from CSC (bullous CSC group) and 122 eyes of 84 patients with chronic CSC without bullous retinal detachment (nonbullous CSC group). METHODS: We performed a retrospective review of clinical and multimethod imaging data of patients who sought treatment from the authors with bullous retinal detachment resulting from CSC between January 2010 and November 2015. Multimethod imaging comprised color photography, fluorescein angiography, fundus autofluorescence, and high-resolution optical coherence tomography. Consecutive cases of chronic CSC without bullous retinal detachment, seen during the same period, comprised a comparative group. MAIN OUTCOME MEASURES: Qualitative and quantitative characteristics of the choroid, retinal pigment epithelium, and retina were compared between the 2 groups. RESULTS: Mean age of the bullous CSC group was 53.8 years. There was no difference in age, visual acuity, corticosteroid use, or the proportion of white patients and men between the 2 groups (all P > 0.132). Peripheral nonperfusion occurred only in eyes with bullous retinal detachment (38% of cases). Retinal pigment epithelial tears were seen in 95% of eyes in the bullous group and none of the eyes in the nonbullous CSC group. The bullous CSC group demonstrated a greater number of pigment epithelial detachments (PEDs) and more eyes demonstrated PEDs with internal hyperreflectivity (both P < 0.016). Mean subfoveal choroidal thickness in the bullous CSC group (463.1±83.1 µm) was not different compared with that of the nonbullous CSC group (400.6±100.6 µm; P = 0.993). More eyes in the bullous CSC group demonstrated hyperreflectivity around large choroidal vessels and at the level of the choriocapillaris on OCT (P < 0.001). Retinal folds and subretinal fibrin were identified in a greater proportion of eyes in the bullous CSC group (both P < 0.001). CONCLUSIONS: Bullous retinal detachment is a rare manifestation of chronic CSC and is characterized by a unique constellation of phenotypic and multimethod imaging features.

Intravitreal cellular infiltrate imaged as punctate spots by spectral-domain optical coherence tomography in eyes with posterior segment inflammatory disease.

PURPOSE: To investigate the posterior segment in cases of clinically evident intraocular inflammation for punctate reflections consistent with that expected to arise from inflammatory cells. METHODS: Patients with ocular inflammatory diseases imaged with spectral-domain optical coherence tomography (SD-OCT) were retrospectively reviewed. RESULTS: There were 7 patients with mean age of 66.7 years, and the diagnosis was toxoplasmosis in 5 eyes, multiple evanescent white dot syndrome in 1 eye, and posttraumatic outer retinitis in 1 eye. At baseline, the SD-OCT showed vitreous cells as numerous punctate spots in the vitreous in all seven eyes. The SD-OCT also showed similar-sized hyperreflective dots in the retina in all seven eyes. During follow-up, reduced vitreous cellular infiltration was correlated with a decrease in the number of the punctate spots visible by SD-OCT. CONCLUSION: Eyes with intraocular inflammation had SD-OCT images of the vitreous containing punctate spots of a size consistent with that expected from inflammatory cells. Similarly sized punctate spots were seen within the retina in regions of retinitis. Additional characterization of the optical section should permit stereological estimations of actual cell counts per unit volume.

MULTIMODAL IMAGING OF ANGIOID STREAKS ASSOCIATED WITH TURNER SYNDROME.

PURPOSE: To report multimodal imaging in a novel case of angioid streaks in a patient with Turner syndrome with 10-year follow-up. METHODS: Case report of a patient with Turner syndrome and angioid streaks followed at Bellevue Hospital Eye Clinic from 2007 to 2017. Fundus photography, fluorescein angiography, and optical coherence tomography angiography were obtained. RESULTS: Angioid streaks with choroidal neovascularization were noted in this patient with Turner syndrome without other systemic conditions previously correlated with angioid streaks. CONCLUSION: We report a case of angioid streaks with choroidal neovascularization in a patient with Turner syndrome. We demonstrate that angioid streaks, previously associated with pseudoxanthoma elasticum, Ehlers-Danlos syndrome, Paget disease of bone, and hemoglobinopathies, may also be associated with Turner syndrome, and may continue to develop choroidal neovascularization, suggesting the need for careful ophthalmic examination in these patients.

Comprehensive analysis of the candidate genes CCL2, CCR2, and TLR4 in age-related macular degeneration.

PURPOSE: To determine whether variants in the candidate genes TLR4, CCL2, and CCR2 are associated with age-related macular degeneration (AMD). METHODS: This study was performed in two independent Caucasian populations that included 357 cases and 173 controls from the Netherlands and 368 cases and 368 controls from the United States. Exon 4 of the TLR4 gene and the promoter, all exons, and flanking intronic regions of the CCL2 and CCR2 genes were analyzed in the Dutch study and common variants were validated in the U.S. study. Quantitative (q)PCR reactions were performed to evaluate expression of these genes in laser-dissected retinal pigment epithelium from 13 donor AMD and 13 control eyes. RESULTS: Analysis of single nucleotide polymorphisms (SNPs) in the TLR4 gene did not show a significant association between D299G or T399I and AMD, nor did haplotypes containing these variants. Univariate analyses of the SNPs in CCL2 and CCR2 did not demonstrate an association with AMD. For CCR2, haplotype frequencies were not significantly different between cases and controls. For CCL2, one haplotype containing the minor allele of C35C was significantly associated with AMD (P = 0.03), but this did not sustain after adjustment for multiple testing (q = 0.30). Expression analysis did not demonstrate altered RNA expression of CCL2 and CCR2 in the retinal pigment epithelium from AMD eyes (for CCL2 P = 0.62; for CCR2 P = 0.97). CONCLUSIONS: No evidence was found of an association between TLR4, CCR2, and CCL2 and AMD, which implies that the common genetic variation in these genes does not play a significant role in the etiology of AMD.

Pseudo-vitelliform macular detachment and cuticular drusen: exclusion of 6 candidate genes.

PURPOSE: The etiology and genetic cause of pseudo-vitelliform macular detachment with cuticular drusen (PVMD/CD) are unknown; nor is it clear if this phenotype represents a separate disease entity, or is a sub-phenotype of disorders with overlapping clinical presentation. To answer this question, we screened a cohort of patients affected with PVMD/CD for variation in six plausible candidate genes (ABCA4, VMD2, TIMP-3, peripherin/RDS, fibulin 5 (FIBL5) and complement factor H (CFH)) associated with diseases of overlapping phenotypes. METHODS: Twenty-eight patients, diagnosed with pseudo-vitelliform macular detachment and cuticular drusen, were evaluated by clinical examination, fundus photography, fluorescein angiography and autofluorescence imaging. DNA from all study subjects were screened for variants in the ABCA4, VMD2, TIMP-3, peripherin/RDS, FIBL5 and CFH genes by a combination of DHPLC, array screening and direct sequencing. RESULTS: All patients presented with cuticular drusen; pseudo-vitelliform detachment was seen in 21 cases, while atrophic changes following regression of the detachment were seen in the remaining 7 subjects. Visual acuity ranged from 20/20 to CF. The screening revealed an I32V mutation in peripherin/RDS in one patient and 2ABCA4 variants, T897I and G1961E, in 2 more patients. No amino acid-altering variants were detected in VMD2, TIMP-3, and FIBL5 genes. The frequency of the CFH Y402H variant in this cohort corresponded to that detected in the general population. CONCLUSIONS: Screening of 6 candidate genes detected possibly disease-associated mutations in only 3/28 (10.7%) of patients presenting with PVMD/CD, eliminating these genes as causal for this phenotype.

Treatment of conjunctival squamous cell carcinoma with photodynamic therapy.

PURPOSE: The aim of this study was to describe the clinical and angiographic response of squamous cell carcinoma (SCC) of the conjunctiva to treatment with photodynamic therapy (PDT). DESIGN: Interventional case series. METHODS: In a prospective study, three patients (62 to 86 years old) with SCC of the conjunctiva were treated with PDT. Patients received one to three treatments of verteporfin (6 mg/m(2) body surface area, intravenously). The light dose was calculated as 50 J/cm(2). All tumors were irradiated 1 minute after injection. The mean follow-up time was 8.6 months (7 to 12 months). Main outcome measurements were clinical and angiographic response and treatment-related side effects. RESULTS: One week after treatment, angiographic occlusion of tumor vasculature and normal conjunctival vessels was observed in all patients. Tumor regression was noted in all patients 1 month after treatment. Two patients had complete regression (clinical and angiographic observation) after one or two treatments for the entire follow-up time. One tumor involved large aspects of the conjunctiva and cornea. In this case, only the treated areas showed tumor regression. PDT caused minimal temporary local irritation in two patients, and small conjunctival hemorrhages and mild transient chemosis in the three eyes directly after treatment. One patient had infusion-related back pain. CONCLUSION: The preliminary results of this study suggest that PDT may be a valuable addition to the treatment of patients with SCC of the conjunctiva. However, longer follow-up is necessary to assess the duration and degree of tumor control.

Treatment of choroidal melanoma using photodynamic therapy.

PURPOSE: To InternetAdvance publication at ajo.com Feb 26, 2002. investigate the effect of photodynamic therapy using verteporfin on choroidal melanoma. DESIGN: Interventional case series. METHOD: Four patients with choroidal melanoma who showed recurrence or no response after previous brachytherapy and transpupillary thermotherapy were treated with photodynamic therapy. RESULTS: One tumor decreased in size and remained stable for 18 months. One tumor had no growth for 11 months. Two melanomas continued to grow, necessitating enucleation. CONCLUSIONS: Of the four eyes that had failed conventional therapies, two would have been salvaged (to date) with photodynamic therapy. However, additional studies are needed to determine if photodynamic therapy can play a role in the management of choroidal melanoma.

NAVILAS Laser System Focal Laser Treatment for Diabetic Macular Edema - One Year Results of a Case Series.

PURPOSE: To report one year outcomes of focal Navigated Retina Laser Therapy (NAVILAS) for diabetic macular edema (DME). METHODS: Retrospective cohort series of 7 diabetic patients treated with NAVILAS focal laser. Statistical analysis included descriptive and continuous variables (Best-corrected logMAR Visual Acuity and time-domain optical coherence tomography (OCT) parameters) which were compared using a non-parametric procedure, the Friedman tests for repeated measures. A p-value of less than 0.05 was considered to denote statistical significance. RESULTS: diabetic patients (4 male; 3 female) with an average age of 60.8 years (range 48-85 years) were included. All treated eyes were phakic; patients had an average hemoglobin A1C of 9.1 (range 7.8-11.7) at baseline and 8.0 (range 7.4-8.4) at 12 months. Six of the 7 patients had intravitreal bevacizumab injections prior to focal laser treatment with 1 patient having had more than 1 prior injection (total 3). At 12 months, median logMAR improved from 0.695 (± interquartile range 0.574) to 0.477 (± 0.573, p <0.001). OCT median central foveal thickness decreased from 248 (± 112) to 220 µm (± 41, p <0.001); total macular volume decreased from 7.84 (± 0.8) to 7.44 mm3 (± 0.7, p = 0.117); and largest macular subfield thickness decreased from 354 (± 116) to 289 µm (± 42, p <0.001). All patients were treated without complications. CONCLUSIONS: Focal NAVILAS showed to be safe and effective in treating DME with improvement in visual acuity and macular edema on OCT over 12 months in this case series. In clinical practice, combined treatment with focal laser including NAVILAS and anti-vascular endothelial growth factor may provide long-term improvement in DME.

Elastin rs2301995 polymorphism is not associated with polypoidal choroidal vasculopathy in caucasians.

PURPOSE: To investigate the association of the rs2301995 haplotype-tagging single nucleotide polymorphism (htSNP) in the elastin gene (ELN) with polypoidal choroidal vasculopathy (PCV) in European-American patients. METHODS: Association analysis of allele and genotype frequencies, determined by TaqMan assays, was performed for the rs2301995 haplotype-tagging single nucleotide polymorphism (htSNP) in the ELN locus in fifty-six patients with PCV, 368 patients with advanced age-related macular degeneration (AMD) and 368 age- and ethnically-matched unaffected controls. RESULTS: The ELN rs2301995 SNP was not statistically significantly associated with the PCV phenotype (P = 0.9). The frequency of the minor allele of the rs2301995 SNP was practically identical in the PCV, AMD and control groups (6.3% vs. 5.4% vs. 7.1%). CONCLUSION: The PCV phenotype in European-American patients is not associated with rs2301995 SNP in the ELN locus.

Macular dystrophy in Heimler syndrome.

PURPOSE: To describe the retinal imaging findings in the index patient with Heimler syndrome (OMIM #234580). DESIGN: Non-interventional case report. METHODS: A 29-year-old woman with Heimler syndrome developed bilateral vision loss. Fluorescein angiography (FA), fundus autofluorescence (FAF), spectral domain optical coherence tomography (SD-OCT) and electroretinography (ERG) were performed to assess the retinal anatomy and function. RESULTS: FA showed mottling of the retinal pigment epithelium (RPE) in the posterior pole and periphery of the retina. FAF revealed hyper and hypoautofluorescent dots corresponding to the RPE mottling observed on FA. SD-OCT documented loss of the inner/outer segments boundary, and RPE thinning. ERG testing excluded generalized rod-cone dysfunction. CONCLUSION: We report an adult-onset macular dystrophy in one of the previously reported patients with Heimler syndrome and hypothesize that this syndrome is probably an expression of a ciliopathy.

Incidence of new choroidal neovascularization in fellow eyes of patients treated in the MARINA and ANCHOR trials.

PURPOSE: To explore whether monthly intravitreal ranibizumab injections are associated with a lower rate of new choroidal neovascularization (CNV) in fellow eyes of patients with unilateral neovascular age-related macular degeneration. DESIGN: Retrospective data analysis of randomized, controlled clinical trials. METHODS: Incidence of new CNV in fellow eyes was calculated at 12 and 24 months from 2 clinical trials (the Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular Age-Related Macular Degeneration [MARINA] study and the Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in Age-Related Macular Degeneration [ANCHOR] study), based on fluorescein angiographic reading center criteria and investigator evaluation. Patients treated with monthly ranibizumab (0.3 and 0.5 mg) were compared with those receiving a sham injection (MARINA) or photodynamic therapy (ANCHOR). RESULTS: In MARINA, new CNV developed in fellow eyes in 20.3% of the 0.3-mg ranibizumab group by 12 months and in 30.4% by 24 months. The conversion rate in the 0.5-mg ranibizumab group was 21.1% and 38.0% by 12 and 24 months, respectively. In the sham group, 26.4% converted by 12 months and 36.3% converted by 24 months. In ANCHOR, fellow eyes in 15.9% of the 0.3-mg ranibizumab group converted by 12 months and fellow eyes in 23.8% converted by 24 months. The conversion rate in the 0.5-mg ranibizumab group was 24.3% and 35.1% by 12 and 24 months, respectively. In the photodynamic therapy group, 25.4% converted by 12 months and 38.8% converted by 24 months. Differences in conversion rates at 12 and 24 months between the 0.3-mg or 0.5-mg ranibizumab groups and respective controls (sham or photodynamic therapy) were not statistically significant. CONCLUSIONS: Results of this study do not support the hypothesis that monthly ranibizumab injections reduce the rate of CNV development in untreated fellow eyes.

Refractory neovascular age-related macular degeneration secondary to polypoidal choroidal vasculopathy.

PURPOSE: To describe a neovascular pattern associated with treatment-refractory neovascular age-related macular degeneration (AMD). DESIGN: A retrospective observational case series. SETTING: Clinical practice. PATIENT POPULATION: Twelve eyes of 12 patients with neovascular AMD in which a poor anatomic response to anti-vascular endothelial growth factor (VEGF) therapy was related to polypoidal choroidal vasculopathy (PCV). OBSERVATION PROCEDURE: Slit-lamp biomicroscopy, optical coherence tomography, fluorescein and indocyanine green angiography. MAIN OUTCOME MEASURES: Snellen visual acuity (VA), anatomic response to therapy including presence or absence of retinal edema, hemorrhage, and lipid exudates. RESULTS: New or persistent PCV was identified in a cohort of patients demonstrating increasing macular exudation despite regular intravitreal ranibizumab (Lucentis; Genentech Inc, South San Francisco, California, USA) or bevacizumab (Avastin; Genentech Inc) injections for a minimum of 6 months. Treatment with verteporfin photodynamic therapy (PDT), PDT/anti-VEGF combination therapy, or continued anti-VEGF monotherapy resulted in complete resolution of exudation in 9 of 12 patients and partial resolution of exudation in the remaining 3 patients. CONCLUSION: Treatment-refractory neovascular AMD may harbor vascular abnormalities such as PCV. Modifications in therapeutic protocols may be indicated in order to improve visual and anatomic outcomes in this population.

Central serous chorioretinopathy and peripheral retinal neovascularization.

PURPOSE: To report a case of bullous retinal detachment complicated by peripheral retinal ischemia and neovascularization in a patient with chronic central serous chorioretinopathy (CSC). RESULTS: Focal laser photocoagulation to the active retinal pigment epithelial leaks in the posterior pole resulted in resolution of the bullous detachment and regression of the retinal neovascularization. CONCLUSIONS: Patients with chronic CSC and a large, dependent serous detachment with peripheral retinal ischemia and neovascularization may be managed by focal treatment to active pigment epithelial leaks alone. This could spare patients of the adverse effects associated with widespread laser treatment and reduce the risk of visual loss due to vitreous hemorrhage and/or more severe complications resulting from progressive retinal ischemia.

Phenotypic features of patients with NR2E3 mutations.

OBJECTIVE: To describe the phenotypes of 5 patients with NR2E3 mutations. METHODS: Two patients with familial and 3 with sporadic early-onset nyctalopia and retinal pigment abnormalities were screened for mutations in the NR2E3 gene (OMIM 604485). The clinical course, fundus features, visual field test results, and fluorescein angiographic and electrophysiologic findings were compared. RESULTS: Three different mutations in NR2E3 were identified: R311Q and 2 novel mutations--missense change Q350R and an in-frame deletion of phenylalanine at position 71 (delF71) in exon 2. Three patients who were homozygous for R311Q had posterior subcapsular cataracts and a concentric ring of round pigment clumps. Electroretinograms were extinguished. A fourth patient, a 24-year-old man who was heterozygotic for R311Q and Q350R, had Goldmann-Favre syndrome. A fifth patient, a 10-year-old boy with heterozygotic mutations R311Q and delF71, had diminished foveal reflexes and subtle pigmentary changes, perhaps a forme fruste of Goldmann-Favre syndrome. Both of these patients had an identical spectral electroretinographic pattern characteristic of enhanced S-cone syndrome. CONCLUSIONS: Molecular genetic testing is essential for establishing the correct diagnosis in patients with NR2E3 mutations because of the variable phenotype associated with these degenerations. Two novel NR2E3 mutations are described that are associated with Goldmann-Favre syndrome and enhanced S-cone syndrome.

Long-term follow-up in enhanced s-cone syndrome.

PURPOSE: To report the long-term follow-up of a case of enhanced S-cone syndrome (ESCS). METHODS: Retrospective chart review. RESULTS: The patient was misdiagnosed with atypical retinitis pigmentosa at 17 years of age. Twenty-seven years of follow-up showed slow deterioration but relative preservation of vision. The most striking clinical feature was the formation of a ring of heavy round pigment clumping around the vascular arcades. Electroretinogram was reported as extinguished in advanced stages of the condition. Genetic testing revealed the most common mutation of the NR2E3 gene reported in the Goldmann-Favre syndrome/ESCS entity. CONCLUSION: Visual acuity can be relatively preserved over the course of ESCS. In advanced stages, genetic testing can be a valuable diagnostic tool.

Vitreomacular adhesion in active and end-stage age-related macular degeneration.

PURPOSE: To evaluate vitreomacular relations in different stages of age-related macular degeneration (AMD) without the influence of genetics and environmental factors. DESIGN: Retrospective, observational case series. METHODS: This was a multicenter study consisting of 29 previously untreated subjects with active exudative (wet) AMD in one eye and active nonexudative (dry) AMD in the fellow eye who were compared with 10 previously untreated subjects with end-stage geographic atrophy in one eye and an end-stage fibrotic (disciform) scar in the fellow eye. All subjects were studied with ultrasonography to identify the presence of posterior vitreous detachment (PVD) and by optical coherence tomography to detect vitreomacular adhesion (VMA). RESULTS: The incidence of PVD in eyes with nonexudative AMD was 20 (69%) of 29, compared with 6 (21%) of 29 with active exudative AMD (P = .002). VMA was present in 11 (38%) of 29 of eyes with exudative AMD and in only 3 (10%) of 29 eyes with nonexudative AMD (P = .008). The incidence of PVD in geographic atrophy was 7 (70%) of 10, compared with 4 (40%) of 10 with disciform scar (P = .44). VMA was present in 2 (20%) of 10 eyes with disciform scars and in 0 (0%) of 10 eyes with geographic atrophy (P = .48). CONCLUSIONS: PVD may protect against exudative AMD, whereas VMA may promote exudative AMD. This phenomenon is not evident in end-stage disease because of an increased incidence of PVD and a decreased incidence of VMA in eyes with disciform scars. Genetic and environmental factors do not seem to influence these observations.

Type 3 neovascularization: the expanded spectrum of retinal angiomatous proliferation.

BACKGROUND: Retinal angiomatous proliferation (RAP) is a distinct form of neovascularization in patients with age-related macular degeneration. Lacking definitive sequential histopathologic evidence of its intraretinal versus choroidal origin, the clinical observations of early stages of RAP lesions may provide clues to help further expand our understanding of this entity. METHODS: Five eyes of four patients with early Stage 1 RAP were examined. Fundus photography, fluorescein and indocyanine green angiography as well as time-domain and spectral-domain optical coherence tomography were performed. Images were assessed to determine the characteristics of neovascularization in early stage RAP lesions and the response of the lesions to treatment or observation. RESULTS: The analysis of the selected cases suggests a choroidal origin of the neovascular complex with the early formation of a retinal choroidal anastomosis without evidence of underlying occult Type 1 neovascularization. Three eyes responded to a single treatment with intravitreal ranibizumab (0.5 mg) and 2 eyes (1 patient) resolved spontaneously without treatment. CONCLUSION: The neovascularization in RAP may originate not only from deep retinal capillaries but also from the choroid. We therefore propose the more descriptive term "Type 3 neovascularization" for this entity to emphasize the intraretinal location of the vascular complex and distinguish this type from the two types of neovascularization previously described by J. Donald Gass in his classic text.