Purpose: To analyze the visual and anatomical outcomes for eyes with rhegmatogenous retinal detachment (RRD) and advanced proliferative vitreoretinopathy (PVR) undergoing giant peripheral retinotomy (GPR) using 25-gauge pars plana vitrectomy (PPV). Methods: In this retrospective multi-center study, patients with RRD with either anteroposterior or circumferential retinal shortening and advanced PVR requiring more than 90-degree GPR with/without relaxing retinotomy were included. Subjects of either gender, any age group, and with complete surgical notes were included. Outcome measures of the study included anatomical success (i.e. complete retinal re-attachment) at 6 months using survival analysis, visual outcomes, and post-operative complications. Results: Forty-one eyes of 41 patients (33 males) with a mean age of 44.9 ± 21.4 years were included. At 6 months follow-up, anatomical success was seen in 29 eyes (70.7%) with a cumulative re-attachment rate of 66% (95% confidence interval = 48 = 79%). All re-detachments occurred at ≤6 months with a peak at 4–6 months (n = 9). Twenty-three eyes (56%) achieved ambulatory vision (5/200) or better. Direct perfluorocarbon liquid-silicone oil exchange was performed in 20 eyes. Intra-operative complications included persistent retinal folds (2 eyes), subretinal air (1 eye), and subretinal bleed (1 eye). Eleven eyes (26.8%) developed secondary glaucoma (2 eyes required a drainage device), and hypotony of ≤6 mmHg was noted in 3 eyes (7.3%). Corneal decompensation was noted in 8 eyes (19.5%), and 3 eyes (7.3%) underwent re-surgery for re-RRD. Conclusion: After GPR using small gauge PPV, two-thirds achieve anatomical success, and over half have ambulatory vision, but overall post-operative complications can occur in more than half of the eyes.

Lentigo maligna melanoma (LMM) is a type of invasive melanoma. When LMM comprises periocular and ocular tissues, sequential multimodality treatments may be needed to avoid wide surgical excisions. We report the case of a recurrent LMM after multiple excisions elsewhere that involved the entire lower eyelid and lateral part of the upper eyelid skin, extending to the lower tarsal conjunctiva and conjunctival fornix. It was successfully controlled by a multistep approach using orthovoltage radiotherapy, topical chemotherapy, and cryotherapy, saving the patient from exenteration. The patient is still in disease-free status in the fourth year after multistep approach.

Purpose: Uveal melanoma extension to the central nervous system (CNS) is exceedingly rare, and can occur through optic nerve invasion. We report a rare clinical case that presented with cauda equina syndrome as the initial manifestation of metastasis of choroidal melanoma, and showed neurotropic extension by histopathology. Our patient did not demonstrate any evidence of systemic metastasis otherwise. Observations: A 60-year-old male patient with treated choroidal melanoma in his right eye, with presumed clinical control, developed radiation-induced neovascular glaucoma refractory to medical therapy. The eye required enucleation for pain control. One month post-enucleation, he presented to the emergency department with severe abdominal pain, urine retention, constipation, and leg weakness. Magnetic resonance imaging (MRI) of the spine showed extensive leptomeningeal involvement along the entire spinal cord and the cauda equina. On further inquisition, the patient noted prior visual field defect in the contralateral eye. Brain MRI revealed intracranial metastasis with chiasmal involvement. The patient underwent radiotherapy for the brain and spine to improve his symptoms, and was ultimately transferred to palliative care. Conclusion and importance: Optic nerve invasion in uveal melanoma may lead to neurotropic spread of melanoma cells with risk of intracranial and spinal cord metastasis. Neurological symptoms should raise the suspicion of clinicians regarding this complication, which is associated with increased melanoma-related mortality.

Purpose: To describe a novel surgical technique to remove retained subfoveal perfluorocarbon liquid (PFCL). Methods: After setting up for 23-G pars plana vitrectomy, a 38-G flexible-tip macular hydrodissection cannula connected to the automated viscous fluid infusion kit was used to create a small retinotomy approximately 700 μm to 800 μm inferior to the fovea and induce macular detachment involving the retained PFCL bubble. The flexible cannula was bent at its junction with the shaft and was carefully advanced through the same retinotomy into the subretinal space to access and directly aspirate the retained subfoveal PFCL bubble. Fluid–air exchange was then performed, and surgery was concluded. Results: The retained subfoveal PFCL bubble was successfully removed with restoration of normal foveal architecture on optical coherence tomography and with objective and subjective improvement of central vision. Conclusion: We report a novel surgical technique combining macular detachment with direct aspiration of the retained subfoveal PFCL without direct perforation of the foveal center. This technique may provide an alternative approach to manage this difficult complication.

A 50-year-old male patient was referred for an assessment of a choroidal lesion in the right eye. He also noticed a rapidly growing caruncle lesion about 2 weeks prior to his visit. His medical history was remarkable for metastatic diseases from clear cell renal carcinoma 1 year before. On ophthalmic evaluation, his visual acuity was 20/20 in both eyes. Anterior segment examination of the right eye showed a red protruding mass at the caruncle [Fig. 1]. Dilated fundus examination demonstrated an amelanotic choroidal lesion at the inferior temporal arcade [Fig. 2]. Ultrasound examination identified a dome-shaped choroidal tumor, with medium internal reflectivity [Fig. 3]. The left eye examination was normal. The caruncle tumor was excised totally. Histopathological examination revealed nests of clear cells with abundant cytoplasm, which confirmed a metastatic renal cell carcinoma (RCC) [Fig. 4]. The right eye was treated with radiotherapy in addition to the second line of systemic targeted therapy. There is no recurrence of conjunctival tumor or choroidal tumors 18 months after treatment [Fig. 5].Figure 1: Anterior segment examination of the right eye showed a red protruding mass at caruncleFigure 2: Dilated fundus examination demonstrated an amelanotic choroidal lesion measuring 5 mm in diameter at inferior temporal fundusFigure 3: Ultrasound examination revealed a domed shaped choroidal tumor, 2.9 mm in thickness with variable internal reflectivityFigure 4: The histopathological examination of the excised caruncle tumor revealed nests of clear cells with abundant cytoplasm, which was conclusive of a metastatic renal cell carcinoma in the caruncleFigure 5: There is no recurrence of conjunctival tumorDiscussion Choroidal metastasis from RCC accounts for only 3% of all choroidal metastases.[123] There were only three cases of conjunctival metastasis from RCC reported in the literature.[45] Two cases presented with a unilateral conjunctival mass as the first presentation of RCC. The third case presented with bilateral choroidal metastases from RCC and developed bilateral conjunctival metastases 6 months later. This is a patient who has an advanced stage of RCC, which is refractory to first-line targeted therapy and immunotherapy. The biopsy of the tumor at caruncle confirmed the nature of the intraocular tumor. To the best of our knowledge, this is the first case to describe concurrent conjunctival and choroidal metastases from RCC, which may represent a more aggressive phenotype of RCC, and requires close monitoring of advanced disease. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Purpose: To evaluate the thickness of individual retinal layers in eyes with resolved diabetic macular edema (DME) after treatment with ranibizumab (RBZ). Methods: Spectral-domain optical coherence tomography (OCT) scans of 25 eyes (25 patients) with DME that had been treated with RBZ (and shown resolution of edema as evident by the absence of fluid in a high-resolution grid placed on the fovea) were acquired using Spectralis HRA + OCTTM. Thickness measurements of individual layers were calculated using papillomacular bundle (PMB), central subfield, and inner- and outer-ring Early Treatment Diabetic Retinopathy Study (ETDRS) grids. Measurements were compared to 45 normal eyes with no known retinal disease. A post-hoc analysis was done correlating visual acuity (VA) with individual retinal layer thickness. Results: Full retinal thickness (FRT) was thinner than normal individuals across all 4 grids. There were similarities and differences among the 4 grids; however, PMB and inner-ring ETDRS grids displayed the most resemblance. The VA significantly correlated with the FRT measured in PMB (p = 0.004), central subfield (p = 0.02), and inner-ring (p = 0.006) ETDRS. Conclusions: Segmentation of OCT scans revealed significant differences in the overall thickness of the retina and of individual retinal layers in patients with resolved DME. PMB grid showed a stronger correlation between affected retinal layers and VA compared to ETDRS. PMB also showed significance with VA in layers that were shown to be not significant in ETDRS grid.

Interferons are cytokines that regulate the host’s response to viral infection, particularly in the setting of the immunologic response to the hepatitis C virus (HCV). While the virus has the ability to evade the host’s innate and specific immunity, exogenous interferon-α with combined ribavirin, treatments have been found to achieve a significant sustained viral response in subgroups of patients with chronic HCV. One of the major side effects of interferon-α is an ocular retinopathy characterized by flame-shaped hemorrhages and cotton wool spots visualized on funduscopic examination. There have been documented cases of more severe side effects including optic nerve and retinal artery damage; however, these instances are the minority. We sought to investigate the literature surrounding interferon-induced retinopathy, clinically correlate our findings with two recent cases, and provide recommendations for practitioners who continue to manage chronic HCV patients using interferon-α with combined ribavirin treatments.

Objective: To report the anatomical and visual outcomes of patients with thick submacular hemorrhage (SMH) treated with pars plane vitrectomy (PPV), subretinal tissue plasminogen activator (t-PA), and pneumatic displacement. Design: Single-centre, retrospective case series. Participants: A total of 99 eyes of 99 consecutive patients with thick SMH secondary to any underlying etiology treated with PPV with subretinal t-PA and pneumatic displacement by 6 vitreoretinal surgeons at St. Michael's Hospital, Toronto, between July 2004 and August 2016. Methods: All medical records and colour fundus photographs were reviewed for data collection. Blood displacement was evaluated at follow-up visits and classified as complete, partial, or none. Main outcome measures included blood displacement at final follow-up, postoperative Snellen best-corrected visual acuities (BCVA), and complication and recurrence rates. Results: Patients had a mean age of 77.7 +/- 12.3 years and were followed up for an average of 18.4 +/- 22.3 months. Wet age-related macular degeneration was the most common etiology associated with thick SMH (80.8%). Complete blood displacement was observed by final follow-up in 85.9% of the cases, partial displacement in 12.1%, and none in 2.0%. Mean logMAR BCVA improved from 2.03 +/- 0.81 (Snellen 20/2143) at baseline to 1.80 +/- 1.00 (Snellen 20/1262; p = 0.009) at final follow-up, and baseline BCVA was a significant predictor of final BCVA (p < 0.001). Early postoperative complications included vitreous hemorrhage in 13 eyes and rhegmatogenous retinal detachment in 8. Recurrent SMH was observed in 12 cases. Conclusions: Vitrectomy with subretinal t-PA and pneumatic displacement seems to be an effective treatment for SMH in terms of blood displacement and visual outcomes.

Die Neutralisation vom VEGF-A hat sich in der Behandlung der feuchten altersbedingten Makuladegeneration (AMD) durchgesetzt. Zur Verbesserung der Therapie werden antiVEGF-A-kombinierte Therapieansätze beforscht, die zusätzliche pathologische Mechanismen unterbinden. In klinischen Studien wie Fovista [1] oder ONYX [2] wird versucht, die Stabilität neuer Gefäße zu vermindern. Komplementfaktoren wären weitere mögliche effektive Targets. Die Bedeutung des Komplements zeigt sich am CD46, einem von fast jeder Zelle exprimierten Rezeptor, der verhindert, dass das Komplementsystem die eigenen Zellen angreift. In der Studie von Lyzogubov et al. zeigt eine CD46 Knock-out-Maus alle Symptome der AMD, vor allem geographische Atrophie. Wie ein Komplement das retinale Pigmentepithel (RPE) schädigt, konnten die Autoren Brandstetter et al. zeigen. Das Komplementprodukt C5a «primed» RPE Zellen zur Ausbildung eines Inflammasoms, das die RPE-Zellfunktionen in einem entzündlichen Phänotyp ändert. Änderungen der Zellfunktion durch Inflammasome sind durch einen Regulator des Zellmetabolismus, den mTOR (mammalian Target of Rapamycin) verknüpft. Tatsächlich konnten Ma et al. zeigen, dass mTOR-Hemmung die chorioidale Neovaskularisation im Mausmodell effektiv reduzieren kann. Fazit für Klinik ist, dass die Kombinationstherapie erhebliche Verbesserungen der bisherigen Anti-VEGF-A-Therapie ermöglicht, wie aktuelle klinische Studien zeigen. Untersuchungen zu Mechanismen der lokalen Komplement-Aktivierung zeigen neue Targets auf. Prof. Dr. Olaf Strauß olaf.strauss@charite.de

Retinochoroidal vascular diseases are the leading causes of blindness in the developed world. They include diabetic retinopathy (DR), retinal vein occlusion, retinopathy of prematurity, age-related macular degeneration (AMD), and pathological myopia, among many others. Several different therapies are currently under consideration for the aforementioned disorders. In the following section, agents targeting platelet-derived growth factor (PDGF) are discussed as a potential therapeutic option for retinochoroidal vascular diseases. PDGF plays an important role in the angiogenesis cascade that is activated in retinochoroidal vascular diseases. The mechanism of action, side effects, efficacy, and the potential synergistic role of these agents in combination with other treatment options is discussed. The future of treatment of retinochoroidal vascular diseases, particularly AMD, has become more exciting due to agents such as PDGF antagonists.

Retinochoroidale Gefäßerkrankungen sind die häufigste Ursache für Erblindung in den Industrieländern. Zur Gruppe dieser Erkrankungen zählen neben vielen anderen die diabetische Retinopathie, der retinale Venenverschluss, Frühgeborenen-Retinopathie, die altersbedingte Makuladegeneration (AMD) und die pathologische Myopie. Verschiedene Therapien werden derzeit in der Behandlung dieser Erkrankungen erprobt. Im vorliegenden Artikel werden gegen den Wachstumsfaktor PDGF (Platelet-Derived Growth Factor) gerichtete Wirkstoffe als potenzielle neue Behandlungsoptionen bei Gefäßerkrankungen der Netz- und Aderhaut vorgestellt. PDGF spielt eine wichtige Rolle in der Angiogenese-Kaskade, die bei retinochoroidalen Gefäßerkrankungen aktiviert wird. Nachstehend wird auf den Wirkmechanismus, die Nebenwirkungen, die Wirksamkeit und die potenzielle synergistische Rolle dieser Wirkstoffe in Kombination mit anderen Behandlungsansätzen eingegangen. Wirkstoffe wie PDGF-Antagonisten bieten spannende Perspektiven für die zukünftige Behandlung retinochoroidaler Gefäßerkrankungen, insbesondere der neovaskulären AMD.

Sarwar, Salman MD; Hanout, Mostafa MD; Sadiq, Mohammad A. MD; Soliman, Mohamed K. MD; Agarwal, Aniruddha MD; Do, Diana V. MD; Nguyen, Quan Dong MD, MSc; Sepah, Yasir J. MBBS Author Information

Vascular diseases of the retina such as diabetic retinopathy and vascular occlusions account for a large proportion of visual morbidity and blindness worldwide. The role of vitreous in the pathogenesis of these conditions has been increasingly recognized. Despite advances in the surgical technique of pars plana vitrectomy, the use of intravitreal agents for the lysis of vitreous has received attention, guided largely by promising results from the trials involving patients with non-vascular retinal diseases such as vitreomacular traction. The purpose of this review is to provide a comprehensive summary of the present knowledge on pathophysiologic basis of pharmacologic vitreolysis and its efficacy in vascular diseases of the retina. A review of completed and ongoing clinical trials will be presented, along with insights into future directions of this therapy.

Purpose To assess cone density as a marker of early signs of retinopathy in patients with type II diabetes mellitus. Methods An adaptive optics (AO) retinal camera (rtx1™; Imagine Eyes, Orsay, France) was used to acquire images of parafoveal cones from patients with type II diabetes mellitus with or without retinopathy and from healthy controls with no known systemic or ocular disease. Cone mosaic was captured at 0° and 2°eccentricities along the horizontal and vertical meridians. The density of the parafoveal cones was calculated within 100×100-μm squares located at 500-μm from the foveal center along the orthogonal meridians. Manual corrections of the automated counting were then performed by 2 masked graders. Cone density measurements were evaluated with ANOVA that consisted of one between-subjects factor, stage of retinopathy and the within-subject factors. The ANOVA model included a complex covariance structure to account for correlations between the levels of the within-subject factors. Results Ten healthy participants (20 eyes) and 25 patients (29 eyes) with type II diabetes mellitus were recruited in the study. The mean (± standard deviation [SD]) age of the healthy participants (Control group), patients with diabetes without retinopathy (No DR group), and patients with diabetic retinopathy (DR group) was 55 ± 8, 53 ± 8, and 52 ± 9 years, respectively. The cone density was significantly lower in the moderate nonproliferative diabetic retinopathy (NPDR) and severe NPDR/proliferative DR groups compared to the Control, No DR, and mild NPDR groups (P < 0.05). No correlation was found between cone density and the level of hemoglobin A1c (HbA1c) or the duration of diabetes. Conclusions The extent of photoreceptor loss on AO imaging may correlate positively with severity of DR in patients with type II diabetes mellitus. Photoreceptor loss may be more pronounced among patients with advanced stages of DR due to higher risk of macular edema and its sequelae.

BACKGROUND:Central vision loss caused by age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries. Neovascular AMD is characterized by choroidal neovascularization (CNV). Growth of new blood vessels in patients with neovascular AMD is driven by a complex process that involves a signal protein called vascular endothelial growth factor A (VEGF-A). Anti-VEGF drugs that block this protein include ranibizumab, bevacizumab, and aflibercept.OBJECTIVES:To assess and compare the effectiveness and safety of intravitreal injections of aflibercept versus ranibizumab, bevacizumab, or sham for treatment of patients with neovascular AMD.SEARCH METHODS:We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (Issue 11, 2015), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2015), EMBASE (January 1980 to November 2015), PubMed (1948 to November 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to November 2015), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (last searched December 4, 2014), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on November 30, 2015.SELECTION CRITERIA:We included randomized controlled trials (RCTs) in which aflibercept monotherapy was compared with ranibizumab, bevacizumab, or sham for participants with neovascular AMD who were treatment-naive.DATA COLLECTION AND ANALYSIS:We used standard methodological procedures of The Cochrane Collaboration for screening, data abstraction, and study assessment. Two review authors independently screened records, abstracted data, and assessed risk of bias of included studies; we resolved discrepancies by discussion or with the help of a third review author when needed.MAIN RESULTS:We included two RCTs (total of 2457 participants, 2457 eyes). Trial participants had neovascular AMD with active subfoveal choroidal neovascular lesions. Both trials followed the same protocol and compared aflibercept at various doses versus ranibizumab, but they were carried out in different countries. One trial enrolled participants from the United States and Canada, and the second trial was conducted at 172 sites in Europe, Asia Pacific, Latin America, and the Middle East. The overall quality of the evidence was high, and included trials were at low risk for most bias domains assessed; however, both trials were funded by the manufacturers of aflibercept. For the purposes of analysis, we combined aflibercept groups regardless of dosing and analyzed them as a single group.Visual acuity outcomes were similar between aflibercept and ranibizumab groups; at one year, participants in the aflibercept groups showed mean change in best-corrected visual acuity (BCVA) from baseline similar to that of participants in the ranibizumab groups (mean difference (MD) -0.15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, 95% confidence interval (95% CI) -1.47 to 1.17; high-quality evidence). At two years, the mean change in BCVA from baseline was 7.2 ETDRS letters for aflibercept groups versus 7.9 for ranibizumab groups. Sufficient data were not available for calculation of confidence intervals.The proportion of participants who gained 15 or more letters of BCVA by one year of follow-up was approximately 32% for both aflibercept and ranibizumab (RR 0.97, 95% CI 0.85 to 1.11; high-quality evidence), and by two years of follow-up was approximately 31% (RR 0.98, 95% CI 0.85 to 1.12; high-quality evidence). Similar small proportions of participants in the aflibercept and ranibizumab groups lost 15 or more letters of BCVA at one year (RR 0.89, 95% CI 0.61 to 1.30; high-quality evidence); this outcome was not reported for two-year follow-up. Data were not reported on the proportion of participants with BCVA worse than 20/200 at one- or two-year follow-up.Participants treated with aflibercept or ranibizumab showed similar improvement in morphological outcomes, as assessed from images (central retinal thickness and CNV size). At one year, the proportion of eyes that achieved dry retina was similar between aflibercept and ranibizumab groups (absence of cystic intraretinal fluid and subretinal fluid on optical coherence tomography (OCT); RR 1.06, 95% CI 0.98 to 1.14; high-quality evidence). In addition, investigators reported no difference in reduction of CNV area between aflibercept- and ranibizumab-treated eyes at one year (MD -0.24 mm(2), 95% CI -0.78 to 0.29; high-quality evidence). Data were not reported for the proportion of eyes with absence of leakage on fluorescein angiography at one- or two-year follow-up.Overall, occurrence of serious systemic adverse events was similar and comparable in aflibercept- and ranibizumab-treated groups at one year (RR 0.99, 95% CI 0.79 to 1.25). Risk of any serious ocular adverse event was lower in the aflibercept group than in the ranibizumab group, but the risk estimate is imprecise (RR 0.62, 95% CI 0.36 to 1.07). As the result of imprecision, we graded the quality of evidence for all adverse events as moderate.AUTHORS' CONCLUSIONS:Results of this review document the comparative effectiveness of aflibercept versus ranibizumab for visual acuity and morphological outcomes in eyes with neovascular AMD. Current available information on adverse effects of each medication suggests that the safety profile of aflibercept is comparable with that of ranibizumab; however, the number of participants who experienced adverse events was small, leading to imprecise estimates of absolute and relative effect sizes. The eight-week dosing regimen of aflibercept represents reduced treatment requirements in comparison with monthly dosing regimens and thus has the potential to reduce treatment burden and risks associated with frequent injections.