A Real-World, Multicenter, 6-Month Prospective Study in Greece of the Effectiveness and Safety of Ranibizumab in Patients with Age-Related Macular Degeneration Who Have Inadequately Responded to Aflibercept: The "ELEVATE" Study.

Purpose: Real-world evidence on short-term outcomes of ranibizumab in wet age-related macular degeneration (wAMD) following inadequate response to aflibercept is scarce. This study aimed to evaluate the functional and anatomic effects of switching to ranibizumab in cases of wAMD previously treated with aflibercept with inadequate response. Patients and Methods: Prospective, observational study performed in eight ophthalmology hospital/private clinics in Greece, enrolling consented patients with active wAMD, ≥50 years-old, who had initiated ranibizumab ≥28 days and <2 months after their last aflibercept injection. Data were collected at enrollment, and at 1, 3 and 6 months post-treatment onset (post-baseline). Results: Between September-2015 and November-2017, 103 eligible patients (56.3% females; mean age: 74.8±8.6 years) were consecutively enrolled. The age at AMD diagnosis in the study eye was 71.3±8.8 years. Aflibercept (median of 5 injections received over 11.3 months) had been discontinued for anatomical (in 69.9%) and/or functional (38.8%) reasons. At baseline (median: 24.3 months after wAMD diagnosis), choroidal neovascularization was occult in 69.1% of evaluable study eyes; 60.2% of the study eyes had pigment epithelial detachment (PED); 42.7% cysts; 21.4% fibrosis; 66.0% subretinal, and 59.2% intraretinal fluid. At 6 months post-baseline: a median of 3 ranibizumab injections (range: 1-6) had been received; the best-corrected visual acuity (BCVA)≥0 letter gain rate was 81.8%; the BCVA ≥15 letter gain rate was 17.0%; BCVA gain was 3.2 letters [mean increase: 3.2±10.0 letters; median: 0.0; p = 0.002]; PED greatest basal diameter (GBD; median: 1470.5 µm) also decreased (median decrease: 114.0 µm; p = 0.019). Baseline central retinal thickness (CRT; median: 312.0 µm) remained unchanged. One patient permanently discontinued ranibizumab due to adverse event occurrence, assessed as not causally related to ranibizumab. There were no ranibizumab-related adverse reactions. Conclusion: Six-month treatment with ranibizumab in aflibercept inadequate responders led to visual acuity and PED GBD improvements, with no statistically significant CRT change.

Detection of retinal pigment epithelium detachment from OCT images using multiscale Gaussian filtering.

Macular diseases, including neovascular age-related macular degeneration (nvAMD), are leading causes of irreversible blindness and visual impairment. One prominent feature of nvAMD is the detachment of the retinal pigment epithelium. The aim of this study is to implement an automated method for the segmentation of the pigment epithelial detachment (PED) using optical coherence tomography (OCT). OCT datasets from 8 patients with nvAMD were acquired during multiple sessions. At each session, 17 images with a resolution of 1020 × 640 pixels were obtained. The images were segmented using Gaussian filtering and template matching for the detection of the upper and lower border of the PED, respectively. The results of the method were compared with the ones obtained from the manual segmentation of the images by an expert. Four well-known metrics were used to evaluate the performance of the method with respect to the manual segmentation, resulting in high scores of consistency. Furthermore, the proposed method was also compared with four other well-known methods providing similar or superior performance.

The photoreceptor layer as a prognostic factor for visual acuity in the secondary epiretinal membrane after retinal detachment surgery: imaging analysis by spectral-domain optical coherence tomography.

PURPOSE: To study the prognostic factors that influence best-corrected visual acuity (BCVA) outcome in patients with secondary epiretinal membrane (ERM) after retinal detachment surgery. DESIGN: Retrospective case series. METHODS: Forty-two patients with ERM were divided into macula-on and macula-off groups based on the macular status before retinal detachment surgery and were studied using the same spectral-domain optical coherence tomography device. Several variables, including the integrity of the external limiting membrane (ELM), the status of the photoreceptor inner segment/outer segment (IS/OS) junction line, and central foveal thickness were evaluated in 17 treated and 25 untreated patients. Linear regression analysis was used to determine the best combination of all variables affecting BCVA. RESULTS: Final BCVA was significantly better in macula-on and macula-off eyes with intact ELMs and IS/OS junction lines (0.35 ± 0.18 logarithm of the minimal angle of resolution [logMAR] and 0.51 ± 0.17 logMAR, respectively) than in macula-off eyes with disrupted or absent ELMs and IS/OS junction lines (0.83 ± 0.17 logMAR and 1.04 ± 0.05 logMAR, respectively; P < .001, analysis of variance). Final BCVA also was better in the treated group than in the controls (0.55 ± 0.31 logMAR and 0.73 ± 0.26 logMAR, respectively; P = .05, t test). ELM and IS/OS junction line integrity were the main variables significantly affecting the final BCVA outcome (ß = 0.42; P = .006, linear regression analysis). Disruption of the ELM and IS/OS junction line was observed in 21 of the 42 cases studied. CONCLUSIONS: ERM secondary to retinal detachment surgery is accompanied by a high incidence (50%) of IS/OS junction line and ELM disruption. Among the variables studied, the condition of the IS/OS junction layer and the ELM are the main factors that predict final BCVA after ERM peeling.

Retinoschisis detected with handheld spectral-domain optical coherence tomography in neonates with advanced retinopathy of prematurity.

OBJECTIVES: The recent development of handheld spectral-domain optical coherence tomography (HHSD-OCT) has enabled us to obtain high-resolution retinal scans of premature infants with retinopathy of prematurity (ROP). The purpose of this study is to document HHSD-OCT findings in laser-treated neonates with progressive ROP. METHODS: This is a retrospective consecutive case series of 3 patients with progressive ROP despite laser photocoagulation. All patients were transferred from peripheral neonatal intensive care units (NICUs) to the Children's Hospital Los Angeles. All patients had a complete ocular examination, fundus photography, fluorescein angiography, and HHSD-OCT. RESULTS: All 3 patients had active progressive ROP despite prior laser photocoagulation. Of the 6 eyes, 1 was excluded from the study because it had an exudative retinal detachment following laser photocoagulation. Retinal detachment was not detected on clinical examination in the 5 remaining eyes, although there was vitreoretinal traction at the ridges of 3 of the 5 eyes. The HHSD-OCT identified presumed retinoschisis in all 5 study eyes. CONCLUSIONS: Tractional retinoschisis may be an important finding in progressive laser-treated ROP, made possible by use of the HHSD-OCT. This finding may have significant implications for how we classify and treat patients whose ROP is progressing despite laser treatment. Furthermore, the use of the HHSD-OCT can provide valuable insight into the interaction of the retina, vitreous, and ridge in patients with progressive ROP, and it allows shallow detachments and retinoschisis to be diagnosed earlier and more accurately than would otherwise be possible.

Intravitreal administration of the anti-TNF monoclonal antibody infliximab in the rabbit.

BACKGROUND: Tumor necrosis factor (TNF) is known to play an important role in various immune-mediated ocular diseases; intravenous administration of the anti-TNF monoclonal antibody infliximab has proved beneficial in such cases. Since intravitreal injection (when available) is a substitute for systemic administration of various drugs targeting the eye, we aimed to evaluate the safety of intravitreal injection of infliximab in the rabbit eye. METHODS: Seven groups of New Zealand white rabbits (four animals in each group) received a single unilateral intravitreal injection (0.1 ml) of increasing doses of infliximab (namely 1, 2, 5, 8, 10 or 20 mg infliximab [Remicade]) or a sham injection respectively. Slit-lamp biomicroscopy, fundoscopy and electrophysiology recordings, i.e. scotopic, photopic and flicker responses, were performed at baseline and after 1, 5, 10, 15, 30 and 45 days. Infliximab-injected eyes were compared with sham-injected and with uninjected fellow eyes (n = 28). Animals were euthanized on day 45 for histopathological examination of the retinas. RESULTS: Clinical examination and electrophysiological testing were consistently unremarkable after either sham or 1 mg or 2 mg infliximab injections. In contrast, electrophysiological recordings were significantly reduced in a dose-dependent manner from day 1 through day 45, after 5, 8, 10 and 20 mg infliximab injections. Flicker responses were the most sensitive in detecting the lower toxic dose of 5 mg. Histopathological findings were similar in uninjected and sham-injected eyes, as well as after 1 mg or 2 mg infliximab injections. Consistent with the functional abnormalities, retinal deformities and diffuse edema were observed after injection of 5 mg or higher doses of infliximab. CONCLUSIONS: Intravitreal infliximab may be safely administered up to a dose of 2 mg in the rabbit eye. Such doses can be used in the design of future clinical trials assessing the effects of infliximab for selected patients with immune-mediated ocular conditions.

Analysis of recurrence patterns associated with toxoplasmic retinochoroiditis.

PURPOSE: Toxoplasmic retinochoroiditis is thought to recur randomly. We sought to determine whether there is, instead, a longitudinal pattern of recurrences and to identify risk factors for recurrence. DESIGN: Longitudinal cohort study. METHODS: We collected the following data for 143 patients with toxoplasmic retinochoroiditis in The Netherlands: gender, first affected eye, age at first episode, mode of Toxoplasma gondii infection (congenital vs postnatal), treatment history, and presence of retinal scars at initial examination. For each episode, we determined age, duration since first episode, and interval since previous episode. We estimated the relationship between disease-free interval after an episode and recurrence risk. The influence of host and disease factors on recurrence risk was analyzed using Cox regression with frailty modeling for correlated intrapatient recurrence times. We performed a Monte Carlo test for occurrence of clusters after prolonged disease-free intervals. RESULTS: Follow-up ranged from 0.3 to 41 years (323 episodes in first-affected eyes). Recurrence risk was highest immediately after an episode, then decreased with increasing disease-free intervals, a pattern consistent with clustering. Relative risk (RR) of recurrence declined 72% (RR, 0.28; 95% confidence interval [CI], 0.22 to 0.36; P < .001) with each 10-year interval since first episode, and declined 15% (RR, 0.85; 95% CI, 0.71 to 1.01; P = .06) for each 10-year increase in age at first episode. Patients more than 40 years of age were at higher risk of recurrence than younger patients (RR, 1.74; 95% CI, 1.06 to 2.86; P = .03). Clusters of episodes occurred after prolonged disease-free intervals. CONCLUSIONS: Toxoplasmic retinochoroiditis occurs in clusters over time. Recurrence risk is influenced by patient age and duration of infection.

Outcomes associated with ganciclovir implants in patients with AIDS-related cytomegalovirus retinitis.

PURPOSE: To investigate complications associated with ganciclovir implants used to treat AIDS-related cytomegalovirus (CMV) retinitis, and to identify factors that predict poor outcomes. DESIGN: Retrospective chart review. PARTICIPANTS: Consecutive patients with AIDS-related CMV retinitis from 3 clinical facilities who underwent implantation procedures during the period January 1, 1995 through December 31, 2001. METHODS: Baseline for each patient was the date of the first implantation procedure performed during the study period by one of the facilities' surgeons (index implant). Medical and ophthalmological data were collected at baseline and at specific time points after baseline. The dates on which additional implantation procedures were performed and the dates on which complications or vision loss were identified were also recorded. Relationships between potential risk factors and outcomes were studied by Kaplan-Meier analyses and Cox proportional hazards regression models. MAIN OUTCOME MEASURES: Primary outcome measures included postoperative complications specifically related to or possibly related to ganciclovir implants. A secondary outcome measure was vision loss after implantation procedures. RESULTS: The charts of 174 patients (one study eye per patient; 279 implants) were reviewed. Median follow-up was 14.4 months (range, 0-7 years). Complications specifically related to implants occurred throughout follow-up at a rate of 0.064 events per patient-year. Complications possibly related to implants occurred at an overall rate of 0.377 per patient-year, but seemed to be more common during the first 2 years after baseline. During the first 2 years of follow-up, retinal detachments occurred at a rate of 0.156 events per patient-year. The cumulative risk of vision loss (> or =3 lines of Snellen visual acuity) at 7 years was 70%. Poor outcomes were associated with disease factors (size and activity of lesions), lack of highly active antiretroviral therapy (HAART), and lack of HAART-associated immune reconstitution, but not with surgical factors or implant-specific complications. CONCLUSIONS: Complications specifically associated with ganciclovir implants can occur many years after implantation procedures, but the incidence of such complications is low. Continued vision loss is not attributable directly to complications of implants in most cases. This information will help in planning of treatment strategies for CMV retinitis in long-term survivors of human immunodeficiency virus disease.

Intravenous foscarnet in the management of acyclovir-resistant herpes simplex virus type 2 in acute retinal necrosis in children.

BACKGROUND: Diagnosis and management of Acute Retinal Necrosis (ARN) in children that does not respond to systemic acyclovir treatment can be challenging. We report two cases of ARN secondary to herpes simplex virus (HSV) type 2 that was resistant to acyclovir but was treated successfully with intravenous foscarnet. CASE REPORT: Two children diagnosed with ARN failed to show clinical response to systemic acyclovir treatment. Both cases had histories of previous HSV infections and vitreous taps positive for HSV-2. Both were converted to systemic foscarnet treatment with successful control of the retinitis and satisfactory visual outcomes. CONCLUSIONS: Systemic foscarnet can be effective in the management of pediatric acute retinal necrosis caused by HSV-2 when there is an atypical response to conventional acyclovir treatment.

Anterior segment complications associated with scleral buckling.

This article discusses the early and late postoperative complications of scleral buckling involving the anterior segment of the eye. Emphasis is placed on the incidence, pathogenesis, clinical presentation, and treatment of each complication. Preventive measures are also discussed.