Tom G. Sheidow

Outcome results in macular hole surgery: An evaluation of internal limiting membrane peeling with and without indocyanine green

PURPOSE To evaluate the anatomic closure rate and visual outcome in patients undergoing pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling with and without indocyanine green (ICG) enhancement. DESIGN Retrospective, noncomparative interventional case series. PARTICIPANTS One hundred ninety-three consecutive patients (204 eyes) seen at the Barnes Retina Institute with the clinical diagnosis of macular hole who underwent PPV between January 1998 and December 2000. INTERVENTION A consecutive series of 97 patients undergoing PPV with or without unilateral epiretinal membrane removal without ILM peeling (group 1), 44 patients with PPV and ILM peeling without ICG (group 2), and 35 patients with ICG-assisted ILM peeling (group 3). RESULTS Overall, 86.4% of the holes closed with one operation, with 75 of 97 (77.3%) eyes in group 1, 43 of 44 (97.7%) eyes in group 2, and 34 of 35 (97.1%) eyes in group 3 (chi(2)= 10.51, P = 0.007). Of the eyes that did not close, 18 patients in group 1 underwent repeat surgery, with 90 of 97 (92.8%) eyes ultimately achieving closure. Visual acuity after surgery was 20/50 or better in 55 of 97 (56.7%) patients, 31 of 44 (70.4%) patients, and 18 of 35 (51.4%) patients in groups 1, 2, and 3, respectively (chi(2) = 3.43, P = 0.18) and increased by 2 or more lines from their preoperative status in 63 of 97 (64.9%) patients, 34 of 44 (77.3%) patients, and 25 of 35 (71.4%) patients, respectively (chi(2)= 2.25, P = 0.32). Multivariate logistic regression demonstrated that use of ILM peeling during vitrectomy increases the chances of developing 20/50 vision or better (odds ratio [OR], 2.4; 95% confidence interval, 1.06-5.45; P = 0.04). No eyes received concurrent cataract extraction with macular hole surgery, but 75 of 166 (45.2%) required cataract extraction postoperatively. Complications included 20 retinal tears, 4 retinal detachments, and 34 patients with postoperative elevations in intraocular pressure (IOP; defined as IOP greater than 30 mmHg). CONCLUSIONS Although this study is limited by the shorter follow-up in patients undergoing ILM peeling with or without ICG relative to the control group, our experience indicates that the use of ILM peeling is associated with a statistically significant improvement in the rate of primary macular hole closure with a single operation.

Safety of ranibizumab in routine clinical practice: 1-year retrospective pooled analysis of four European neovascular AMD registries within the LUMINOUS programme

Purpose Evaluation of 1-year safety profile of intravitreal ranibizumab 0.5 mg in neovascular age-related macular degeneration (NV-AMD) within routine clinical practice. Methods The LUMINOUS programme comprises a prospective observational study assessing ranibizumab ‘real-world’ safety and clinical effectiveness across licensed indications worldwide and an annual retrospective pooled safety analysis from completed NV-AMD ranibizumab registries. 1-year data from four European registries are available. This retrospective pooled safety analysis assessed 1-year incidence rates for safety events of particular interest (key ocular or systemic events possibly related to the injection procedure or vascular endothelial growth factor inhibition) together with treatment exposure. Patients were treated according to local protocols within the ranibizumab licence. Results Data of 4444 patients from registries in Germany (n=3470), the Netherlands (n=243), Belgium (n=260) and Sweden (n=471) were retrospectively pooled. Between 70.4% and 84.4% of enrolled patients completed 1 year of follow-up. Most frequent overall ocular events of particular interest were retinal pigment epithelial tears (27 patients; <1%) and intraocular pressure-related events (12 patients; <0.3%). Most frequent non-ocular event of particular interest was stroke (19 patients; 0.4%); annual incidence of stroke was low across all registries (0.0–0.5%). Conclusions Ranibizumab demonstrated favourable 1-year safety profile for NV-AMD in this routine clinical practice sample, consistent with previous reported trial data. Additional data from a larger patient population are needed to better describe the long-term safety profile of ranibizumab in routine clinical practice and further evaluate risk for infrequent but serious events in ‘real-life’ settings. The 5-year LUMINOUS prospective observational study will address this need.

Expression of vascular endothelial growth factor in uveal melanoma and its correlation with metastasis.

AIMS To evaluate the expression of vascular endothelial growth factor (VEGF) in uveal melanomas and correlate its presence with tumour characteristics and systemic metastasis. METHODS 47 cases of ciliochoroidal melanoma enucleated between 1983 and 1993 were retrieved from the pathology archives at the University of Western Ontario. Paraffin sections stained with haematoxylin and eosin, periodic acid Schiff, and periodic acid Schiff without haematoxylin after bleaching of melanin were examined. The expression of VEGF protein was examined by an immunoalkaline phosphatase method following antigen retrieval, using an antibody to VEGF and vector red as the chromogen. The intensity of VEGF immunoreactivity was graded on a scale of 0–7 and correlated with tumour cell type, tumour size, presence or absence of necrosis, pigmentation, mitotic activity, microvascular density, and microvascular pattern. RESULTS VEGF immunoreactivity was present in 44/47 tumours (94%): the intensity was graded as very weak (1–2) in 29/47 (62%) and as weak or greater in 15/47 (32%). VEGF was also found in the ciliary epithelium, smooth muscle of the ciliary body and iris, retinal ganglion cells, inner photoreceptor segments, and the retinal pigment epithelium. Follow up data were available in 43/47 patients (91.5%), with a median follow up time of 10 years. 16/43 (37%) patients developed metastases. VEGF expression in melanoma was linked to the presence of tumour necrosis and the degree of pigmentation but no statistically significant relation with microvascular pattern, tumour size, or microvascular density was found. There was no statistically significant correlation between VEGF expression and metastasis. CONCLUSIONS Most ciliochoroidal melanomas express VEGF and expression is correlated with the presence of necrosis but not with the occurrence of systemic metastasis or tumour angiogenesis.

Erdheim-Chester disease: two cases of orbital involvement

Erdheim-Chester disease (ECD) is an increasingly recognised form of fibro- inflammatory process characterised by xanthomatous histiocytes containing large amounts of ingested lipid, plasma cells, macrophages and Touton-type giant cells. Ophthalmic involvement in ECD has been reported in only 22 cases. We describe two patients, one presenting with diabetes insipidus and subsequently developing orbital pseudotumours and retroperitoneal fibrosis, the other presenting with exophthalmos and diplopia. The first patient was treated with cladribine and subsequently developed sudden onset of bilateral blindness while the second required radiation therapy for the retro-orbital process and developed radiation retinopathy. These cases typify the variable presentation and course in patients with ECD.

The role of Frizzled-4 mutations in familial exudative vitreoretinopathy and Coats disease

Aim The aim of this study is to assess the role of Frizzled-4 (FZD4) in familial exudative vitreoretinopathy (FEVR) and Coats disease. Methods Tissue samples were collected for DNA extraction and automated DNA sequencing of the two coding exons of FZD4 in both directions. Cases carrying a FZD4 mutation and demonstrating extreme disease severity were selected for direct automated sequencing of all coding exons of LRP5, NDP and TSPAN12. Clinical data were obtained for the purpose of identifying genotype–phenotype correlations. Results 68 probands were diagnosed as having autosomal dominant or sporadic FEVR. Eleven FZD4 mutations (five missense, three deletions, one insertion, two nonsense) were identified. Six of these mutations are novel, and none were found in 346 control chromosomes. In 16 cases of Coats disease, one polymorphism combination was found in two samples: no mutations were detected. No genotype–phenotype correlation emerged. Three severely affected cases with FZD4 mutations failed to show additional mutations in the three other FEVR genes. Conclusion The authors identified 12 FEVR probands with FZD4 mutations. FZD4 mutation screening can be a useful tool especially in mild or atypical cases of FEVR. Germ-line mutations in FZD4 do not appear to be a common cause of Coats disease.

Cystoid macular edema following combined phacoemulsification and vitrectomy for macular hole.

Purpose: To evaluate the incidence of cystoid macular edema (CME) in patients under‐going either combined or consecutive pars plana vitrectomy (PPV) and phacoemulsifica‐tion (PE) for the treatment of macular hole and cataract. Methods: Retrospective review of a consecutive surgical series of 22 patients with idiopathic macular holes. Seven patients underwent combined PPV with air‐fluid‐C3F8 gas exchange and PE with intraocular lens insertion; 15 patients underwent PE subsequent to PPV. Results: Visual acuity improved by 2 or more lines in 3/7 patients in the combined group and in 15/15 in the consecutive group. Of seven patients in the combined group, two required a second PPV for treatment of the macular hole and one declined further treatment. Of importance, 3/7 in the combined group and 1/15 in the consecutive group developed clinical and angiographic CME, all treated successfully with sub‐Tenon’s triamcinolone injections. Conclusions: Both combined PPV/PE and consecutive PPV/PE offer excellent potential therapeutic benefits for the treatment of idiopathic macular holes. The incidence and pathogenesis of CME must be further investigated.

Comparison of outcomes after switching treatment from intravitreal bevacizumab to ranibizumab in neovascular age-related macular degeneration

OBJECTIVE To compare visual acuity and central retinal thickness in patients initially treated with bevacizumab (Avastin) and switched to ranibizumab (Lucentis) for neovascular age-related macular degeneration (AMD). DESIGN A retrospective chart review. PARTICIPANTS This study included 87 eyes from 80 patients over the age of 65 with neovascular AMD. METHODS Patients were initially treated with bevacizumab injections every 6 weeks and then switched to ranibizumab every 4 weeks when it became publicly funded by the Ontario government. Outcomes include comparison of visual acuity and central retinal thickness after bevacizumab treatment, and after switching to ranibizumab. RESULTS Visual acuity improved significantly versus initial baseline values following a treatment course of 3 or more injections of bevacizumab (0.58 logMar, SD = 0.30 vs 0.73 logMar, SD = 0.41; p = 0.0007). Patients then showed a further significant improvement in visual acuity after switching and receiving a course of ranibizumab (0.51 logMar, SD = 0.32) (p = 0.0122). Mean central retinal thickness as measured by optical coherence tomography significantly decreased after a course of bevacizumab (p = 0.0158), and a further decrease was noted after a subsequent course of ranibizumab (p < 0.0001). CONCLUSIONS There was a significant improvement in visual acuity and central retinal thickness in patients with neovascular AMD initially treated with bevacizumab. When these patients were uniformly switched to ranibizumab there was a further significant improvement in visual acuity and a reduction of retinal thickness. It appears that ranibizumab can maintain, or improve the effect achieved after an initial course of bevacizumab.

Digital reader vs print media: the role of digital technology in reading accuracy in age-related macular degeneration

PurposeTo compare patient satisfaction, reading accuracy, and reading speed between digital e-readers (Sony eReader, Apple iPad) and standard paper/print media for patients with stable wet age-related macular degeneration (AMD).MethodsPatients recruited for the study were patients with stable wet AMD, in one or both eyes, who would benefit from a low-vision aid. The selected text sizes by patients reflected the spectrum of low vision in regard to their macular disease. Stability of macular degeneration was assessed on a clinical examination with stable visual acuity. Patients recruited for the study were assessed for reading speeds on both digital readers and standard paper text. Standardized and validated texts for reading speeds were used. Font sizes in the study reflected a spectrum from newsprint to large print books. Patients started with the smallest print size they could read on the standardized paper text. They then used digital readers to read the same size standardized text. Reading speed was calculated as words per minute by the formula (correctly read words/reading time (s)·60). The visual analog scale was completed by patients after reading each passage. These included their assessment on ‘ease of use’ and ‘clarity of print’ for each device and the print paper.ResultsA total of 27 patients were used in the study. Patients consistently read faster (P<0.0003) on the Apple iPad with larger text sizes (size 24 or greater) when compared with paper, and also on the paper compared with the Sony eReader (P<0.03) in all text group sizes. Patients chose the iPad to have the best clarity and the print paper as the easiest to use.ConclusionsThis study has demonstrated that digital devices may have a use in visual rehabilitation for low-vision patients. Devices that have larger display screens and offer high contrast ratios will benefit AMD patients who require larger texts to read.

Long-term Outcomes For Optic Disk Pit Maculopathy After Vitrectomy

Purpose: To evaluate the efficacy of pars plana vitrectomy for congenital optic disk pit maculopathy with various adjuvant techniques, including gas tamponade, internal limiting membrane peel, and temporal optic disk endolaser in a multicenter study with long-term follow-up. Methods: A retrospective chart review was performed to identify eyes that underwent surgical repair for congenital optic disk pits and serous macular detachment with or without macular retinoschisis from four retinal centers across Canada from 2003 to 2013. Data collected included surgeries performed, preoperative and postoperative vision, central retinal thickness, and presence or absence of subretinal fluid. Optical coherence tomography was used to define anatomical success (i.e., foveal reattachment). Results: Thirty-two eyes of 32 patients with optic disk pits and serous macular detachments were identified that had undergone surgical repair. All eyes underwent pars plana vitrectomy and induction of posterior vitreous detachment if one was not present. Additional procedures performed on occasion included internal limiting membrane peel (n = 8), temporal optic disk pits endolaser (n = 7), and gas tamponade (air, C3F8 or SF6; n = 31). After vitrectomy surgery, foveal attachment was achieved in 26 of 32 eyes (81.3%). The average number of surgeries required was 1.4 ± 0.6, with a maximum of 3 vitrectomies (n = 2). Mean change in best-corrected visual acuity was −0.47 ± 0.54 logMAR units, which corresponds to approximately 5 lines of visual improvement (P < 0.001). Median time to reattachment was 416 days. Preoperative vision, preoperative symptom days, and age were not associated with postoperative reattachment. Similarly, internal limiting membrane peel and temporal endolaser were not associated with postoperative reattachment, nor was there a difference between air and SF6 and C3F8 gas tamponade. Elevated preoperative central retinal thickness was associated with a lower chance of postoperative reattachment (P = 0.007) and was also the best prognostic indicator of success (P = 0.039). Conclusion: Vitrectomy for macular detachment due to optic disk pit has good long-term success and results in an improvement in visual acuity. However, adjuvant techniques such as internal limiting membrane peel and temporal endolaser may not improve outcomes, nor does there seem to be a difference between short- and long-acting gases. Patients should be made aware that it can take more than a year and multiple surgeries to achieve foveal reattachment and that increased baseline central retinal thickness is a poor prognostic sign.

Choroidal lymphoma with orbital and optic nerve extension: case and review of literature

A 62-year-old male presented with 1 year of distorted vision OS. His medical history included alcohol and cigarette consumption. Best corrected visual acuity was 20/30 and IOP 16 mm Hg. The anterior chamber and vitreous were clear other than mild asteroid hyalosis. Diffuse retinal pigment epithelium (RPE) changes and macular thickening were present. The right eye was normal (Fig. 1A, B). Intravenous fluorescein angiogram showed nonspecific leakage at the level of the RPE and macular edema. B-scan