There is a subset of eyes with neovascular age-related macular degeneration (AMD) that have persistent exudation despite fixed-interval intravitreous anti–vascular endothelial growth factor (VEGF) injections.
To evaluate the effect of topical dorzolamide hydrochloride–timolol maleate on anatomic and functional outcomes in eyes with neovascular AMD and incomplete response to anti-VEGF therapy.
Design, Setting, and Participants
An exploratory, prospective single-arm interventional study at a tertiary referral academic private practice. Patients with neovascular AMD and persistent macular edema despite fixed-interval intravitreous anti-VEGF therapy were enrolled. Baseline spectral-domain optical coherence tomography and clinical data, including visual acuity and intraocular pressure, were obtained at enrollment and from one visit before enrollment. The study was performed at the Retina Service of Wills Eye Hospital and the offices of Mid Atlantic Retina from February 1, 2015, through September 30, 2015. Patients were followed up for at least 2 visits after enrollment. Central subfield thickness, maximum subretinal fluid height, and maximum pigment epithelial detachment height from spectral-domain optical coherence tomography were recorded at each visit. INTERVENTIONS Enrolled eyes received a regimen of topical dorzolamide-timolol twice daily and continued to receive the same intravitreous anti-VEGF therapy at the same interval as received before enrollment for the duration of the study.
Main Outcomes and Measures
Change in central subfield thicknesswas the primary outcome measure. Changes in maximum subretinal fluid height, maximum pigment epithelial detachment height, and visual acuity were the secondary outcome measures.
Ten patients (10 eyes) completed the study. The mean age of the patients was 78.2 years (age range, 65-91 years), and 6 were male. Eight eyes received intravitreous aflibercept, and 2 eyes received intravitreous ranibizumab. All study eyes had been receiving long-term anti-VEGF therapy with the same medication before study enrollment for a mean of 21.9 injections. The mean central subfield thickness decreased from 419.7 μmat enrollment to 334.1 μm at the final visit (P = .01). The mean maximum subretinal fluid height decreased from 126.6 μmat enrollment to 49.5 μm at the final visit (P = .02). The mean maximum pigment epithelial detachment height decreased from 277.4 μmat enrollment to 239.9 μmat the final visit (P = .12). The mean logMAR visual acuity were 0.54 at enrollment and 0.48 at the final visit (P = .60).
Conclusions and Relevance
These data suggest that topical dorzolamide-timolol may reduce central subfield thickness and subretinal fluid in eyes with persistent exudation despite consistent, fixed-interval intravitreous anti-VEGF treatment for neovascular AMD.
Full Paper: Topical Dorzolamide-Timolol With Intravitreous Anti–Vascular Endothelial Growth Factor for Neovascular Age-Related Macular Degeneration
Diabetic Macular Edema (DME) is the leading cause of visual impairment in patients with diabetic retinopathy.1 In 2010, approximately 20.6 million out of a projected 92.6 million adults with diabetic retinopathy worldwide were estimated to have concurrent DME.2 This global healthcare burden will likely continue to increase at alarming rates, as some models estimate the number of diabetics will double by the year 2030.3
With the Early Treatment Diabetic Retinopathy Study (ETDRS) in the 1980s,4 macular laser photocoagulation became the mainstay of DME management, and it remained the standard of care in the decades that followed. The advent of intravitreal pharmacotherapy agents, primarily driven by the class of vascular endothelial growth factor (VEGF) inhibitors, has since revolutionized how this condition is treated. Validated through the RISE and RIDE phase 3 clinical trials,5 ranibizumab (Lucentis; Genentech, South San Francisco, California, USA) became the first VEGF inhibitor approved by the Food & Drug Administration (FDA) for this indication in 2012.
While off-label, bevacizumab (Avastin; Genentech) has been evaluated through smaller trials, such as the BOLT study.6 Most recently, aflibercept (Eylea; Regeneron, Tarrytown, New York) gained FDA approval to treat DME in July 2014 with the VIVID and VISTA phase 3 clinical trials.7,8
While there is ample evidence supporting the safety and efficacy of the 3 anti-VEGF agents in the management of DME, a head-to-head comparison only recently became available when the Diabetic Retinopathy Clinical Research Network (DRCR) published the 1-year outcomes of its Comparative Effectiveness Study of Intravitreal Aflibercept, Bevacizumab, and Ranibizumab for DME (Protocol T).9 The results demonstrated that when baseline visual acuity (VA) loss was mild (›20/ 40), there was no clinical difference between the 3 medications. However, when the initial acuity loss was more severe (‹20/50), a greater visual benefit was derived from aflibercept.9
Since the FDA approval of aflibercept for DME, and in light of Protocol T’s findings, many retinal specialists are converting eyes from ranibizumab or bevacizumab to aflibercept with the goal of optimizing treatment outcomes, particularly in cases of refractory DME. In the current study, we evaluated the short-term functional and anatomic responses of patients with persistent DME after multiple previous anti-VEGF injections that were converted to aflibercept therapy.
Full Paper: Conversion to Aflibercept After Prior Anti-VEGF Therapy for Persistent Diabetic Macular Edema
To investigate whether lamellar macular holes can be divided into different subgroups.
Retrospective observational case series.
In this institutional study, clinical charts and spectral-domain optical coherence tomography (OCT) images of 102 eyes of 90 consecutive patients diagnosed with lamellar macular hole were reviewed. In OCT imaging, the presence of lamellar macular hole was defined according to the following findings: presence of irregular foveal contour, separation of the layers of the neurosensory retina, and the absence of full-thickness macular defect. Mean outcome was the morphologic and functional characterization of different subtypes of macular hole.
Two different subtypes of lamellar macular hole were identified: tractional and degenerative. The first type, tractional, was diagnosed in 43 eyes, and was characterized by the schitic separation of neurosensory retina between outer plexiform and outer nuclear layers. It often presented with an intact ellipsoid layer and was associated with tractional epiretinal membranes and/or vitreomacular traction. The second type, degenerative, was diagnosed in 48 eyes, and its distinctive traits included the presence of intraretinal cavitation that could affect all retinal layers. It was often associated with nontractional epiretinal proliferation and a retinal “bump.” Moreover, it often presented with early ellipsoidal zone defect and its pathogenesis, although chronic and progressive, remains poorly understood. Eleven eyes shared common features with both tractional and degenerative lamellar macular holes and were classified as mixed lesions.
Degenerative and tractional lamellar macular holes may be 2 distinct clinical entities. A revision of the current concept of lamellar macular holes is needed.
Full Paper: Lamellar Macular Hole: Two Distinct Clinical Entities?
Several studies have focused on the current use of oral fluoroquinolones and the risk for retinal detachment (RD), but the existence of this association is under debate. Given the widespread fluoroquinolone use, investigation of this association is essential.
To assess the association between oral fluoroquinolone use and the risk for RD, including the rhegmatogenous and exudative types.
Design, Setting, and Participants
This case-crossover study included 27 540 adults with RD from French health care databases from July 1, 2010, through December 31, 2013. Patients with a history of RD or retinal break, endophthalmitis, intravitreal injection, choroidal retinal vitreal biopsy, and human immunodeficiency virus infection or those hospitalized within 6 months of RD were excluded. The risk period of primary interest was current use, defined as exposure to fluoroquinolones within 10 days immediately before RD surgery, according to previous findings. Oral fluoroquinolone use was assumed to start on the day the prescription was dispensed.
Main Outcomes and Measures
Exposure to fluoroquinolones during the risk period (1-10 days) compared with the control period (61-180 days). The association was also assessed regarding use in the recent (11-30 days) and past (31-60 days) intermediate risk period, type of fluoroquinolone, and type of RD.
Of the 27 540 eligible patients (57%men; mean [SD] age, 61.5 [13.6] years), 663 patients with RD were exposed to fluoroquinolones during the observation period, corresponding to 80 cases exposed during the 10-day risk period (10 days before RD) and 583 cases exposed during the control period (61-180 days).We found a significant increased risk for RD during the 10-day period after the dispensing of oral fluoroquinolones, with an adjusted odds ratio of 1.46 (95%CI, 1.15-1.87). The risk was significantly increased for rhegmatogenous and exudative RD, with adjusted odds ratios of 1.41 (95%CI, 1.04-1.92) and 2.57 (95%CI, 1.46-4.53), respectively. Recent and past use of fluoroquinolones were not associated with a higher risk for RD, with adjusted odds ratios of 0.94 (95%CI, 0.78-1.14) and 1.06 (95%CI, 0.91-1.24), respectively.
Conclusions and Relevance
Current oral fluoroquinolone use was associated with an increased risk for RD, including the rhegmatogenous and exudative types. These findings, along with the available literature, suggest an association between fluoroquinolone use and the risk for RD. The nature of this association should be further investigated in future studies.
Full Paper: Association Between Oral Fluoroquinolone Use and Retinal Detachment