Neurotrophic keratopathy following rhegmatogenous retinal detachment surgery.

OBJECTIVE: To describe clinical characteristics and visual outcomes of eyes developing neurotrophic keratopathy (NK) following rhegmatogenous retinal detachment (RRD) repair. METHODS: All eyes with NK at Wills Eye Hospital following RRD repair from June 1, 2011, to December 1, 2020 were included. Patients with prior ocular procedures (other than cataract surgery), herpetic keratitis, and diabetes mellitus were excluded. RESULTS: During the study period, 241 patients were diagnosed with NK, and 8179 eyes underwent RRD surgery, giving a 9-year prevalence rate of 0.1% (95% CI, 0.1%-0.2%). Mean age was 53.4 ± 16.6 years during RRD repair and 56.5 ± 13.4 years during NK diagnosis. Mean time to NK diagnosis was 3.0 ± 5.6 years (range, 6 days to 18.8 years). Mean visual acuity before NK was 1.10 ± 0.56 logMAR (20/252 Snellen), and it was 1.01 ± 0.62 logMAR (20/205 Snellen) at final visit (p = 0.75). Six eyes (54.5%) developed NK <1 year following RRD surgery. Mean final visual acuity was 1.01 ± 0.53 logMAR (20/205 Snellen) in this group versus 1.01 ± 0.78 logMAR (20/205 Snellen) in the delayed NK group (p = 1.00). CONCLUSIONS: NK may present acutely or up to several years following surgery, with severity of corneal defects ranging from stage 1 to stage 3 NK. Surgeons should be mindful of the potential for this rare complication following RRD repair.

Creating an Ocular Biofactory: Surgical Approaches in Gene Therapy for Acquired Retinal Diseases.

ABSTRACT: Gene therapy offers the potential to treat inherited retinal disorders and deliver sustained therapy for acquired retinal diseases. In the latter case, host cells can be harnessed to produce non-native proteins that have beneficial properties, such as antivascular endothelial growth factor activity, transforming the eye into an ocular "biofactory." Several gene therapy programs have entered clinical testing for delivery to the vitreous, subretinal, and suprachoroidal space. Improved viral vectors and refined surgical techniques are critical to successful delivery of therapeutic products to the target tissue. In this review, we discuss the development of gene therapy products aimed at acquired retinal diseases and the surgical techniques utilized to achieve targeted delivery.

Endophthalmitis after cataract surgery: an update on recent advances.

PURPOSE OF REVIEW: Prevention and management of postcataract endophthalmitis remain quite relevant for anterior segment and vitreoretinal surgeons. Although the Endophthalmitis Vitrectomy Study, published in 1996, remains the only level 1 evidence for the management of postcataract endophthalmitis, recent advances have resulted in an evolution of practice patterns. The aim of this review is to summarize the literature regarding postcataract endophthalmitis with a focus on the last 18 months. RECENT FINDINGS: The IRIS registry indicates the rates of endophthalmitis are decreasing in the United States, and the outcomes appear to be improving. Intracameral moxifloxacin has become more widely accepted and intracameral vancomycin has been shown to be associated with retinal vasculitis. The role of systemic antibiotics and vitrectomy is unclear and practice patterns vary widely. SUMMARY: Although practice patterns vary, prevention and treatment of endophthalmitis after cataract surgery continues to improve. More uniform guidelines regarding surgical and medical therapy are necessary but the standard of prompt referral to a vitreoretinal specialist for immediate intravitreal antibiotics remains the most important intervention in the management of postcataract endophthalmitis.

Interventional therapy for brain arteriovenous malformations before and after ARUBA.

The ARUBA trial (2014) concluded that medical management alone is superior to medical management plus interventional therapy for the treatment of unruptured brain arteriovenous malformations (bAVMs). This sparked considerable controversy among involved healthcare providers. Here, we evaluated the impact of ARUBA on the volume, type, and treatment modality of bAVMs referred to a large tertiary care center. This was achieved by conducting a retrospective review of a prospectively maintained database of all bAVMs treated at Stanford Health Care and Stanford Children's Health from January 2012 through July 2015. The case volume of bAVMs treated at Stanford has been relatively unchanged in the period of time leading up to and after ARUBA. Furthermore, there has been no significant change in the proportion of unruptured AVMs treated. Although differences existed in types of interventions administered, these differences are best explained by variations in the SM grades of AVMs treated during each study period, rather than by underlying changes in treatment strategy. Additional research is warranted to more thoroughly characterize the impact of ARUBA on the treatment patterns of bAVMS.

Effect of aflibercept on refractory macular edema associated with central retinal vein occlusion.

OBJECTIVE: To report short-term visual and anatomic outcomes of patients who were switched to aflibercept for persistent macular edema associated with central retinal vein occlusion (CRVO). METHODS: Retrospective, consecutive, interventional case series of 17 patients with persistent macular edema secondary to CRVO (defined as intraretinal edema and either <50 µm reduction in central foveal thickness [CFT] or worsening or no improvement in visual acuity [VA] compared to baseline) despite anti-VEGF treatment who were switched to aflibercept treatment. Main outcome measures included VA, anti-VEGF treatment history, and spectral-domain optical coherence tomography evaluation of macular edema and CFT. RESULTS: The mean age was 77 years, and the mean VA at CRVO diagnosis was 20/135 with a CFT of 523.4 µm. Mean number of injections before switching to aflibercept was 12.9 (range: 3-40) and mean number of months of anti-VEGF treatment before switching to aflibercept was 18.7. Mean VA at switch to aflibercept was 20/182 (p = 0.50) with mean CFT of 547.9 µm (p = 0.66). Mean aflibercept injections were 4.0, and mean follow-up from switch to last follow-up was 5.2 months. Final mean VA was 20/115 (p = 0.017), with a CFT of 315.2 µm (p = 0.0012). Of the patients, 35.2% gained ≥3 lines. 29% of patients had complete resolution of macular edema, and the mean change in CFT was -233 µm. CONCLUSIONS: Aflibercept appears to have a beneficial effect on anatomic and VA outcomes in a subset of patients with macular edema secondary to CRVO that is refractory to treatment with bevacizumab and/or ranibizumab.

Management of thick submacular hemorrhage with subretinal tissue plasminogen activator and pneumatic displacement for age-related macular degeneration.

PURPOSE: To evaluate the outcome of pars plana vitrectomy, subretinal tissue plasminogen activator (t-PA) infusion and intraocular gas tamponade with and without postsurgical antivascular endothelial growth factor (VEGF) injection for thick submacular hemorrhage due to exudative age-related macular degeneration (AMD). DESIGN: Retrospective, comparative, interventional case series. METHODS: setting: 2 retina referral centers. The patient population included 101 eyes of 101 patients with neovascular AMD and thick submacular hemorrhage who underwent surgical displacement of the hemorrhage with or without postoperative anti-VEGF injections. Main outcome measures included degree of blood displacement, best and final postoperative visual acuity (VA), and adverse events. Snellen acuity was converted to logMAR for statistical analysis. RESULTS: All patients were followed for a minimum of 3 months (mean, 15.3 months, range, 3-70 months). In 83 (82%) of 101 eyes, the procedure resulted in complete hemorrhage displacement from the fovea. Mean preoperative VA was 20/2255 (2.05 logMAR). The acuity significantly improved to 20/893 (1.65 logMAR) at month 1 (P < 0.001) at month 1; 20/678 (1.53 logMAR) at month 3 (P < 0.001), and 20/1150 (1.76 logMAR) at month 12 (P = 0.002). Best postoperative visual acuity improved by at least 1 line in 83 (82%) of 101 eyes, and 19.6% of eyes gained 3 lines or more at month 3. The visual acuity of the group of eyes that received postoperative anti-VEGF injection (n = 39) showed greater visual acuity improvement 6 months postoperatively compared to the group of eyes that did not receive postoperative anti-VEGF. Postoperative complications included vitreous hemorrhage in 2 eyes, rhegmatogenous retinal detachment in 4 eyes, and recurrent thick subretinal hemorrhage in 6 eyes. CONCLUSIONS: Vitrectomy with subretinal t-PA injection and gas tamponade was found to be relatively effective for displacement of thick submacular hemorrhage with a significant improvement in visual acuity. There is a loss of acuity over time; the addition of postoperative anti-VEGF therapy may help maintain the visual acuity gains.

[Treatment of neovascular age-related macular degeneration with antiangiogenic drugs]. / Tratamento da forma neovascular de degeneração macular relacionada à idade com drogas antiangiogênicas.

Age-related macular degeneration (ARMD) remains a leading cause of blindness in the western world. Several clinical forms of the disease are recognized, whereas choroidal neovascularization (CNV) represents an important manifestation suitable for treatment. The treatment of CNV has been a major focus of research in the past decades, and the first evidence-based established therapy was laser photocoagulation, which reduces the risk of visual loss in extrafoveal lesions. In the late 90's photodynamic therapy has been established as an efficient method for the treatment of predominantly classic and occult CNV. Additional therapies such as macular translocation, submacular surgery, and indocyanine-mediated prothrombosis are currently under investigation in large-scale clinical trials. Molecular biology has recently provided a better comprehension of the pathogenesis of ARMD, and vascular endothelial growth factor (VEGF) was recognized as key mediator in the angiogenesis of CNV-formation. Therefore, the pharmacological approach rose as a key research area to treat CNV. The first FDA-approved agent for CNV-therapy is aptamer pegaptanib sodium (Macugen), which inactivates the key angiogenic isoform VEGF165. Additional VEGF-blockers such as ranibizumab RhuFab V2 (Lucentis) and bevacizumab (Avastin) are under evaluation in major clinical studies. Impressive results of intravitreal bevacizumab were released recently. Moreover, the steroid-derived anecortave acetate as well as the corticosteroid triamcinolone acetate have been proposed as methods for treatment of wet-ARMD. This paper presents the rationale and principles of the pharmacologic antiangiogenic therapy for CNV in ARMD.

Tratamento da forma neovascular de degeneração macular relacionada à idade com drogas antiangiogênicas / Treatment of neovascular age-related macular degeneration with antiangiogenic drugs

Degeneração macular relacionada à idade (DRMI) é a principal causa de cegueira no mundo ocidental. Várias formas clínicas foram reconhecidas, e membrana neovascular coroideana (MNSR) representa manifestação importante passível de tratamento. O tratamento de MNSR tem sido um foco importante de pesquisa nas últimas décadas e a primeira terapia estabelecida baseada em evidência foi a fotocoagulação a laser, que reduziu o risco de perda visual em lesões extrafoveais. No fim da década de 90 a terapia fotodinâmica foi estabelecida como método eficiente de tratamento de MNSR predominantemente clássicas e ocultas. Terapias adicionais como a translocação macular, cirurgia submacular, e protrombose mediada por indocianina verde estão atualmente em investigação em ensaios clínicos em larga escala. A biologia molecular permitiu recentemente uma melhor compreensão da patogênese da DMRI e o fator de crescimento vascular endotelial foi reconhecido como um mediador-chave na angiogênese da formação de MNSR. Portanto, a abordagem farmacológica surge como opção terapêutica no tratamento da MNSR. O primeiro agente terapêutico aprovado pelo FDA é o aptâmero pegaptanib sódio (Macugen®), que inativa a isoforma fundamental para a angiogênese intra-ocular: VEGF165. Outros inativadores de VEGF como ranibizumab RhuFab V2 (Lucentis®) e bevacizumab (Avastin®) estão em avaliação em estudos clínicos. Resultados impressionantes de bevacizumab intravítreo foram liberados recentemente. Adicionalmente, o derivado de esteróides acetato de anecortave, assim como o corticosteróide acetato de triancinolona têm sido propostos como métodos no tratamento de DMRI-neovascular. Este artigo apresenta os princípios e resultados iniciais na terapia antiangiogênica farmacológica da MNSR na DMRI.

Age-related macular degeneration (ARMD) remains a leading cause of blindness in the western world. Several clinical forms of the disease are recognized, whereas choroidal neovascularization (CNV) represents an important manifestation suitable for treatment. The treatment of CNV has been a major focus of research in the past decades, and the first evidence-based established therapy was laser photocoagulation, which reduces the risk of visual loss in extrafoveal lesions. In the late 90's photodynamic therapy has been established as an efficient method for the treatment of predominantly classic and occult CNV. Additional therapies such as macular translocation, submacular surgery, and indocyanine-mediated prothrombosis are currently under investigation in large-scale clinical trials. Molecular biology has recently provided a better comprehension of the pathogenesis of ARMD, and vascular endothelial growth factor (VEGF) was recognized as key mediator in the angiogenesis of CNV-formation. Therefore, the pharmacological approach rose as a key research area to treat CNV. The first FDA-approved agent for CNV-therapy is aptamer pegaptanib sodium (Macugen®), which inactivates the key angiogenic isoform VEGF165. Additional VEGF-blockers such as ranibizumab RhuFab V2 (Lucentis®) and bevacizumab (Avastin®) are under evaluation in major clinical studies. Impressive results of intravitreal bevacizumab were released recently. Moreover, the steroid-derived anecortave acetate as well as the corticosteroid triamcinolone acetate have been proposed as methods for treatment of wet-ARMD. This paper presents the rationale and principles of the pharmacologic antiangiogenic therapy for CNV in ARMD.