Alan R. Berger

Subretinal fibrosis in central serous chorioretinopathy

PURPOSE To report unusual and heretofore unreported visually damaging manifestations of severe central serous chorioretinopathy. METHODS Case studies. RESULTS Each of six male patients (average age, 40 years) had a form of severe central serous chorioretinopathy with at least one eye containing fibrin in the subretinal space that then developed into a subretinal fibrotic scar. Scar formation was followed by a tenting up of the macula, vascularization of the fibrosis (subretinal neovascularization), or a retinal pigment epithelial rip. Four of the seven eyes with subretinal fibrosis had severe visual loss (20/400 or worse). CONCLUSION Subretinal fibrin and other extracellular matrix molecules appear to stimulate the retinal pigment epithelium to undergo fibrous metaplasia, which results in subretinal fibrotic scar formation and other sequelae, all of which can lead to severe visual loss.

An assessment of intraocular pressure rise in patients with gas-filled eyes during simulated air flight

PURPOSE To investigate the safety of aircraft flight for patients with small volumes of residual postoperative intraocular gas. DESIGN Nonrandomized comparative trial. PARTICIPANTS Seventeen eyes (nine gas filled and eight control eyes) of nine patients and one eye of one control subject were tested. METHODS Patients with postoperative intraocular gas and the control subject were tested in the controlled environment of a hypobaric chamber to simulate the cabin depressurization associated with a typical commercial aircraft flight. Before, during, and after a simulated flight, the intraocular pressure (IOP) in the gas-containing and contralateral eyes was tested using the Perkins (Edinburgh, UK) and Tono-Pen XL (Jacksonville, FL) tonometers. MAIN OUTCOME MEASURES The absolute and percentage change in IOP with varied cabin pressurization. RESULTS Of the nine patients with intraocular gas, seven had 10% to 15% gas volume and two had 20% gas volume. In the 10% to 15% gas volume group, the IOP rose by an average of 109% from baseline during ascent to an average cabin altitude of 7429 feet above sea level. The IOP dropped to an average of 30% above baseline IOP during the cruise phase and further decreased to an average of 38% below baseline IOP on return to baseline altitude. In the 20% gas volume group, the IOP rose by an average of 84% from baseline during ascent to an average cabin altitude of 3400 feet above sea level. The IOP dropped to an average of 42% below baseline IOP on return to baseline altitude. The IOP in the contralateral control eyes did not vary with altitude changes. No patient experienced pain or visual loss during the experiments. CONCLUSIONS Our results demonstrate that IOP may rise significantly in gas-filled eyes during simulated air flight, supporting the current conservative recommendation against air travel for most patients with intraocular gas bubbles. Further testing is warranted to develop a more objective measure of intraocular gas volume estimation and to define better the tolerability of aircraft flight for patients with intraocular gas.

Canadian expert consensus: optimal treatment of neovascular age-related macular degeneration.

BACKGROUND New therapeutic approaches, particularly anti-vascular endothelial growth factor (anti-VEGF) therapies, prevent, and in some cases reverse, vision damage caused by age-related macular degeneration (AMD). Unequal access to care across Canada remains a problem for many retina specialists and their patients. OBJECTIVE To develop a consensus concerning the management of patients with exudative age-related macular degeneration (AMD). DESIGN Consensus document. PARTICIPANTS Ten Canadian retina specialists. METHODS The development of a consensus among Canadian experts concerning optimal treatment of AMD began with a review of the clinical evidence, daily practices, existing guidelines, and current national and international approvals and policies. The experts met on June 29, 2010, in Quebec City to discuss their findings and to propose strategies for consensus. RESULTS The result of this expert panel is a consensus proposal for Canadian ophthalmologists and retina specialists who are treating patients with or at risk for developing neovascular AMD. CONCLUSIONS The consensus provides guidelines to aid retina specialists in managing exudative AMD. Currently, ranibizumab is the only agent with sufficient Level I evidence and a Health Canada-approved indication for the treatment of wet AMD. Bevacizumab has been shown to be noninferior in preserving and improving visual acuity when compared to ranibizumab. Potential safety differences between the 2 drugs remain to be elucidated. The positioning of ranibizumab in this therapeutic area will be further defined as additional data for existing and emerging therapies become available. Until then, this agent remains the therapy of choice for individuals with neovascular AMD.

Effectiveness at 1 year of monthly versus variable-dosing intravitreal ranibizumab in the treatment of choroidal neovascularization secondary to age-related macular degeneration.

Purpose To evaluate the visual acuity results of monthly ranibizumab injections compared with a variable-dosing schedule for the treatment of neovascular age-related macular degeneration. Methods A retrospective study that compared two cohorts of consecutive patients. All patients were treatment naive, with baseline visual acuity of 20/400 or better, and completed 12 months of therapy. In the first group all patients received monthly injections. In the other group, after 3 monthly loading doses, a variable-dosing schedule was used, based on a monthly clinical assessment and optical coherence tomography. Results Fifty-six consecutive patients (60 eyes) were included. At 12 months the median number of injections were 12 and 8, respectively, and the mean change in Snellen visual acuity was an improvement of 0.27 logarithm of the minimum angle of resolution in the monthly treated group versus 0.21 logarithm of the minimum angle of resolution improvement in the variable-dosing group (P = 0.53). In the monthly treated group 96.8% of eyes lost <0.3 logarithm of the minimum angle of resolution versus 96.6% of eyes in the variable-dosing group (P = 1.0). Conclusion We were able to show that in our clinical setting patients achieved similar visual acuity results with either monthly injections or with a variable-dosing protocol. There was a trend toward better results with monthly treatment.

AQUEOUS HUMOR CYTOKINE LEVELS AS BIOMARKERS OF DISEASE SEVERITY IN DIABETIC MACULAR EDEMA.

Purpose: To determine whether aqueous cytokine levels correlate with disease severity in diabetic macular edema. Methods: A prospective cross-sectional study of 49 adults with diabetes mellitus, centre-involving diabetic macular edema and central subfield macular thickness ≥310 &mgr;m on spectral domain optical coherence tomography. Clinical examination and aqueous sampling were carried out before an initial injection of ranibizumab. Multiplex immunoassay of sample was carried out for vascular endothelial growth factor, placental growth factor, transforming growth factor beta, intercellular adhesion molecule-1, interleukin (IL)-2, IL-3, IL-6, IL-8, IL-10, IL-17, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, and epidermal growth factor. Multivariate robust regression models were constructed, and adjusted for age, lens status, or severity of retinopathy, and size of foveal avascular zone. Results: Spectral domain optical coherence tomography macular volume was an excellent measure of disease severity, correlating strongly with central subfield macular thickness (P < 0.001), best-corrected Snellen visual acuity (P < 0.001), and baseline diabetic retinopathy severity (P = 0.01). Elevated aqueous intercellular adhesion molecule-1 correlated with greater macular volume (P = 0.002). No aqueous cytokine, including VEGF, correlated with central subfield macular thickness. There was an association between IL-10 levels and best-corrected Snellen visual acuity (P = 0.03). Conclusion: Aqueous intercellular adhesion molecule-1 correlates with disease severity as measured by macular volume on spectral domain optical coherence tomography, and IL-10 is associated with BCVA. Intercellular adhesion molecule-1 may be a clinically useful biomarker for diabetic macular edema severity.

Use of Evicel Fibrin Sealant in Optic Disc Pit-Associated Macular Detachment

Optic disc pit is a rare congenital anomaly of the optic nerve. Retinal detachment is a common complication with poor outcomes. Many surgical alternatives have been described for the treatment of this condition, producing variable results. Herein, the authors describe four cases of optic disc pit-associated macular detachment managed with pars plana vitrectomy, fluid-air exchange, drainage of subretinal fluid through the optic disc pit, temporal peripapillary laser, and application of Evicel fibrin sealant (human) (Ethicon, Bridgewater, NJ) over the optic disc head. Case 1 showed stable visual acuity and improvement of subretinal fluid. Cases 2 and 3 showed visual acuity and subretinal fluid improvements. At the 1-week follow-up visit, Case 4 showed almost total subretinal fluid absorption. The sealant invariably disappeared between 1 and 2 weeks and was tolerated by all patients. This case series suggests that Evicel fibrin sealant may be considered as an adjunctive option in the surgical treatment of optic disc pit-associated maculopathy. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:358-363.].

Bacterial endophthalmitis: 10-year review of the culture and sensitivity patterns of bacterial isolates

OBJECTIVE To examine the spectrum and sensitivity patterns of bacterial isolates derived from all culture-positive aqueous and vitreous samples submitted for culture and sensitivity analysis at our institution over a 10-year period. DESIGN Retrospective cohort study. PARTICIPANTS A total of 368 culture-positive aqueous and vitreous samples from 265 patients were reviewed. METHODS Over a decade extending from January 2000 through December 2009, all culture-positive aqueous and vitreous specimens at our institution were identified. Isolated bacterial pathogens and their in vitro antibiotic sensitivities were analyzed. RESULTS Approximately 86.4% of patients had positive cultures for either staphylococci (Staphylococcus aureus and coagulase-negative staphylococci [CNS]) or streptococci. Gram-negative bacteria were isolated in only 9.8% of patients. From 2000 to 2004, 81.2% and 55.9% of CNS isolates were sensitive to ciprofloxacin and cefazolin, respectively, compared with 41.2% and 23.5% of isolates in the last 5 years. Over the study period, ceftazidime retained 100% efficacy against the gram-negative isolates tested. Vancomycin was 99.6% effective against the gram-positive isolates tested. CONCLUSIONS The microbiology of pathogens in endophthalmitis is evolving, with an increase in streptococcal isolates and a decrease in CNS. The apparent lack of efficacy of conventionally used antibiotics and the emergence of increasingly resistant strains of bacteria may have significant implications in the management of bacterial endophthalmitis.

PROPORTION OF PATIENTS WITH MACULAR HOLE SURGERY WHO WOULD HAVE BEEN FAVORABLE OCRIPLASMIN CANDIDATES: A Retrospective Analysis.

Purpose: To identify favorable ocriplasmin candidates from a cohort of idiopathic full thickness macular hole surgery patients. Methods: The records of patients with full thickness macular hole who underwent pars plana vitrectomy surgery between 2011 and 2015 were reviewed. Clinical data collected included patient demographics, pre- and post-operative Snellen visual acuity, optical coherence tomography findings, and lens status. The authors defined “favorable” ocriplasmin candidates as patients with focal vitreomacular traction, no epiretinal membrane, and hole size ⩽400 &mgr;m. The authors further categorized “optimal” candidates as age ⩽65, phakic, no epiretinal membrane, with focal vitreomacular traction, and hole size ⩽400 &mgr;m. Results: The records of 238 patients were assessed; 30.7% were male while mean age was 68.6 ± 8.3 years. The mean logMAR acuity was 1.2 (Snellen 20/317) preoperatively and 0.90 (Snellen 20/159) postoperatively. Optical coherence tomography findings indicated that 46.5% of the macular holes studied were less than ⩽400 &mgr;m in size, 14.8% had an epiretinal membrane, and 25.3% had vitreomacular traction. A total of 17.7% of study patients were found to be favorable candidates, whereas 3.8% were optimal ocriplasmin candidates. Conclusion: Only a minority of full thickness macular hole surgical candidates in this cohort would be considered favorable ocriplasmin candidates.

Real-world utilization of ranibizumab in wet age-related macular degeneration patients from Canada

Age-related macular degeneration (AMD) affects more than 2 million Canadians and is associated with significant impairment. Although AMD is a degenerative condition linked to aging, the most progressive form is associated with increased vascular endothelial growth factor (VEGF), a potent angiogenic mediator. This has resulted in the development and widespread use of anti-VEGF agents, such as ranibizumab, which was approved for use in wet AMD by the U.S. Food and Drug Administration in 2006 based on the findings from 2 key studies (ANCHOR and MARINA) that demonstrated sustained improvement in visual acuity with monthly dosing. However, some less frequent dosing schedules (such as quarterly) are not as effective. It is therefore important to monitor ranibizumab use in reallife settings in order to assess outcomes in relation to actual prescribing patterns. AURA was a retrospective, observational study that monitored the real-world utilization of ranibizumab in practices across 8 countries (Canada, France, Germany, Ireland, Italy, the Netherlands, the United Kingdom, and Venezuela). In this study, consecutive wet AMD patients who were prescribed ranibizumab by their physicians and who started treatment between January 1 and August 31, 2009, were included and followed up for up to 2.5 years. Resource utilization (number of ranibizumab injections and monitoring visits) and change in visual acuity (measured by Early Treatment Diabetic Retinopathy Study [ETDRS] letters or Snellen with conversion to a standardized letter count) were assessed in accordance with routine clinical practices. A guiding sample size of 399 patients per country was required to estimate the change in visual acuity; however, as Canada recruited 188 patients, the data are presented as descriptive statistics. Two-year outcomes were reported for the effectiveness analysis set (patients who received Z1 dose of anti-VEGF treatment and had Z1 postbaseline assessment of visual acuity for the treated eye). To account for missing data, mean change in visual acuity was assessed using a

Aqueous Humor Cytokine Levels and Anatomic Response to Intravitreal Ranibizumab in Diabetic Macular Edema

Importance Variability in response to anti–vascular endothelial growth factor (VEGF) treatment in diabetic macular edema (DME) remains a significant clinical challenge. Biomarkers could help anticipate responses to anti-VEGF therapy. Objectives To investigate aqueous humor cytokine level changes in response to intravitreal ranibizumab therapy for the management of DME, and to determine the association between baseline aqueous levels and anatomic response. Design, Setting, and Participants In this prospective multicenter cohort study, 49 participants with diabetes mellitus complicated by center-involving DME, with a central subfield thickness of 310 &mgr;m or greater on spectral-domain optical coherence tomography (SD-OCT), were recruited from December 22, 2011, to June 13, 2013 and statistical analysis were performed from March 1, 2017, to June 1, 2017. A total of 48 participants proceeded to follow-up. Interventions Participants received monthly injections of ranibizumab, 0.5 mg, for 3 months. Aqueous fluid for cytokine analysis was obtained at baseline and repeated at the 2-month visit. Multiplex immunoassay was carried out in duplicate for VEGF, placental growth factor, transforming growth factor beta 2, intercellular adhesion molecule 1 (ICAM-1), interleukin 6 (IL-6), IL-8, IL-10, vascular intercellular adhesion molecule, and monocyte chemoattractant protein 1. Main Outcomes and Measures Baseline and 2-month change in aqueous cytokine levels, 3-month change in SD-OCT central subfield thickness and macular volume (MV), and the statistical association between baseline aqueous cytokine levels and these measures of anatomic response to ranibizumab in center-involving DME. Results Among the 48 participants, the mean (SD) age was 61.9 (7.1) years and 36 participants (75.0%) were men. The following cytokines were lower at month 2 vs baseline: ICAM-1 (median change, −190.88; interquartile range [IQR], −634.20 to −26.54; P < .001), VEGF (median change, −639.45; IQR, −1040.61 to −502.61; P < .001), placental growth factor (median change, −1.31; IQR, −5.99 to −0.01; P < .001), IL-6 (median change, −38.61; IQR, −166.72 to −2.80; P < .001), and monocyte chemoattractant protein 1 (median change, −90.13; IQR, −382.74 to 109.47; P = .01). When controlling for age, foveal avascular zone size, and severity of retinopathy, multiple linear regression determined that increasing baseline aqueous ICAM-1 was associated with a favorable anatomic response, in terms of reduced SD-OCT MV at 3 months (every additional 100 pg/mL of baseline ICAM-1 was associated with a reduction of 0.0379 mm3; P = .01). Conversely, increasing baseline aqueous VEGF was associated with a less favorable SD-OCT MV response at 3 months (every additional 100 pg/mL of baseline VEGF was associated with an increase of 0.0731 mm3; P = .02) and was associated with lower odds of being a central subfield thickness responder (odds ratio, 0.868; 95% CI, 0.755-0.998). Conclusions and Relevance Elevated aqueous ICAM-1 and reduced VEGF levels at baseline are associated with a favorable anatomic response to ranibizumab in DME, although there is not always direct correlation between anatomic and visual acuity response.