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.

Anecortave acetate treatment for retinal angiomatous proliferation: a pilot study.

PURPOSE: The purpose of this study was to evaluate anecortave acetate treatment of retinal angiomatous proliferation (RAP), a neovascular form of age-related macular degeneration, with specific regard to inhibition of neovascularization and maintenance of vision. METHODS: Thirty-four patients with RAP with any stage of neovascularization were randomized 1:1:1 for treatment with three different quantities (30 mg, 15 mg, 3 mg) of anecortave acetate sterile suspension for juxtascleral administration. Best-corrected visual acuity (Early Treatment Diabetic Retinopathy Study chart), intraocular pressure measurement, biomicroscopy, funduscopy, digital fluorescein, and indocyanine green angiography were recorded at baseline and at 3 months. A 6-month retreatment interval was established for this study with a follow-up of 12 months. In selected patients optical coherence tomography was performed. The outcomes were mean changes in visual acuity and lesion size at 1 year. RESULTS: The detachment of the neurosensory retina and retinal pigment epithelium improved in all eyes, but all neovascular lesions increased in size. Vision loss occurred in the majority of study eyes (22 out of 34 eyes, 64.7%) independent of the concentration administered. CONCLUSION: The results suggest that a posterior juxtascleral injection of anecortave acetate reduces capillary permeability in patients with RAP. However, in spite of improvement of the exudation there is a progression of neovascularization and a significant loss of vision in all these patients. Like other monotherapeutic methods used to treat this variant of neovascular age-related macular degeneration, anecortave acetate alone does not appear to benefit these patients. Future studies should investigate a combination form of therapy.

Anecortave acetate for the treatment of idiopathic perifoveal telangiectasia: a pilot study.

PURPOSE: To investigate the use of anecortave acetate, a new angiostatic cortisene, for the treatment of the leakage and/or neovascularization associated with idiopathic perifoveal telangiectasia (IPT) in an open label prospective pilot study. METHODS: Seven eyes of six patients were treated with posterior juxtascleral administration of anecortave acetate delivered adjacent to the macula using a specially designed curved cannula. A full clinical examination and fluorescein angiography were performed at baseline and at 3-month intervals. The primary efficacy outcome for this pilot study was the mean change in visual acuity (Early Treatment Diabetic Retinopathy Study) from baseline. RESULTS: The visual acuity remained unchanged in two eyes of two patients with nonproliferative disease after 24 months. The five eyes of four patients presenting with subretinal neovascularization, the proliferative stage of IPT, showed stabilization or improvement of lesion size, resolution of leakage, and stabilization of vision at last follow-up. CONCLUSION: The results of this study suggest that anecortave acetate may inhibit retinal and subretinal permeability as well as neovascular proliferation in patients with IPT. A larger study accordingly should be designed in the future to evaluate the effectiveness and treatment of IPT with this drug.

Enhanced visualization of acute macular neuroretinopathy by Heidelberg Retina Tomography.

We report Heidelberg Retina Tomography (HRT) findings in a case of bilateral acute macular neuroretinopathy in a 22-year-old man. In addition to fundus photography, fluorescein and indocyanine green angiography, and visual field testing, HRT scans of the macula were performed early in the disease and at a follow up of 2 months. We found typical paracentral scotomata in visual field testing corresponding to sharply delineated, hyporeflective areas of the macula as visualized in HRT II scans. Those lesions were almost invisible on regular fundus photographs. Angiography results were unremarkable. The lesion size decreased over time. The visibility of the lesions was markedly enhanced by HRT scans, thus the diagnosis and follow up of acute macular neuroretinopathy could be facilitated by this non-invasive imaging technique.

Sequenced combined intravitreal triamcinolone and indocyanine green angiography-guided photodynamic therapy for retinal angiomatous proliferation.

OBJECTIVE: To study sequenced combined therapy using intravitreal triamcinolone acetonide followed by photodynamic therapy for the treatment of retinal angiomatous proliferation. METHODS: Patients newly diagnosed as having retinal angiomatous proliferation underwent intravitreal triamcinolone injection to reduce intraretinal and subretinal exudation, followed 7 to 14 days later by indocyanine green angiography-guided photodynamic therapy with verteporfin. Complete ocular examination, fluorescein angiography, indocyanine green angiography, and optical coherence tomography were performed at baseline and at standard intervals thereafter. RESULTS: Twenty-seven eyes of 26 patients underwent this sequenced combined treatment and were followed up for 12 months. The triamcinolone injection reduced the cystoid edema before photodynamic therapy. Complete resolution of the angiographic leakage was achieved in 89% of eyes. Visual acuity improved in 37% and was stable in 52% of eyes. Eight eyes developed recurrent leakage after 3 to 11 months. Complete resolution of leakage was observed after subsequent treatment. CONCLUSIONS: This sequenced combined treatment in patients with retinal angiomatous proliferation was effective in reducing or eliminating the edema, achieving rapid regression of neovascularization, and stabilizing or improving visual acuity. To our knowledge, no study to date has achieved such promising results in the management of retinal angiomatous proliferation. A randomized clinical trial is under way to compare sequential and simultaneous combined therapy.

Coats' disease diagnosed in adulthood.

PURPOSE: To investigate the manifestations and clinical course of Coats' disease diagnosed in adulthood and to describe the characteristics of patients who develop it. DESIGN: Retrospective observational case series. PARTICIPANTS: Thirteen eyes of 13 patients with Coats' disease diagnosed after age 35 years. METHODS: All patients examined in the authors' referral practices for Coats' disease diagnosed after the age of 35 years were identified. Patients with a history of radiation exposure, intraocular inflammation, retinal vascular occlusion, or Coats' response were excluded. A review of their historical, clinical, and fluorescein angiographic features and demographics was performed. RESULTS: There were 13 patients with a mean age at diagnosis of 50 years (range, 36-79) and a mean follow-up of 5.8 years (range, 0-17). These patients manifested many findings typical of Coats' disease, including the unilateral nature of the disease (13/13 patients), male predominance (12/13), vascular telangiectasis, lipid exudation, macular edema, and areas of capillary nonperfusion with adjacent webs of filigreelike capillaries. Disease was limited to < or =6 clock hours in 10 of 13 patients (76.9%), did not generally involve the retinal vasculature anterior to the equator, and showed limited potential to expand during the follow-up period. A localized hemorrhage was noted in 10 of 13 patients (76.9%), almost always near larger aneurysmal dilatations. Limited exudative detachment of the retina was seen in 4 eyes, 3 of which responded to localized laser photocoagulation. One patient had subretinal fluid seen on ocular coherence tomography that did not require treatment. On average, patients lost 2.1 lines of visual acuity during the follow-up period; 6 patients had a decline in vision, 2 patients had improved vision, and 3 patients had stable vision. No patient had end-stage findings of Coats' disease, such as iris neovascularization or total exudative detachment. CONCLUSIONS: Coats' disease can first be diagnosed in adulthood with retinal vascular abnormalities similar to those seen in younger patients. There are a number of important differences in disease manifestation in adults, including limited area of involvement, slower apparent progression of disease, and hemorrhage near larger vascular dilatations.

Photoscreening for diabetic retinopathy: a comparison of image quality between film photography and digital imaging.

PURPOSE: Retinal images from patients attending an urban screening centre before and after the transition from film photography to digital image acquisition were analysed for quality of image. METHODS: A total of 1946 diabetic patients, aged 12-92 years (mean 55.6 +/- 14.88 years), were included in this retrospective study of retinal screening techniques. Each imaging group was subdivided into age-matched groups. In all subjects pupils were pharmacologically dilated before photography. The images were reviewed by the same three experienced observers and graded at the time of screening from grade 1 (excellent quality) to grade 4 (unreadable). RESULTS: Of 938 patients in the film group, 31.3% had excellent images, 38.2% good, 22.7% poor and 7.8% were unreadable. Of the 1008 patients in the digital imaging group, 25.3% had excellent images, 46.3% good, 14.6% poor and 13.8% were unreadable. A significant difference was observed in patients over 65 years of age who exhibited a threefold increase in failure rate with digital imaging (33.7% v 11.3%)(P < 0.0001). CONCLUSION: In this study population a statistically significant degradation of image quality was observed in those older than 65 years following transition to digital photography. This has implications for service provision planning.

Comparison of endothelial cell count using confocal and contact specular microscopy.

Precise examination of the corneal endothelium has become increasingly important due to the growing number of intraocular and corneal procedures. The purpose of this study was to compare prospectively the corneal endothelial cell count in normal eyes obtained by confocal and specular microscopy. Central corneal endothelial cell densities of 42 eyes from 42 patients were measured by confocal and contact specular microscopy. Endothelial cells were analyzed with the same software in a manual, an automated and a semi-automated mode. The mean endothelial cell density obtained by confocal microscopy was (in the manual, automated and semi-automated modes) 3,069 +/- 285, 2,791 +/- 344 and 3,077 +/- 286 cells/mm(2), and obtained by specular microscopy 3,076 +/- 298, 2,796 +/- 271 and 3,082 +/- 282 cells/m(2), respectively. No statistically significant difference of endothelial cell density between confocal and specular microscopy was found. Endothelial cell count was significantly lower in the automated than in the semi-automated and manual analysis both with confocal and with specular microscopy. In conclusion, endothelial cell count measurements with confocal and contact specular microscopy are comparable.