Bascom Palmer Researchers Identify Impact of Zika Virus on the Eye Researchers at Bascom Palmer Eye Institute pinpointed the impact of the Zika virus on the eye in a study published Sept. 21, in JAMA Ophthalmology... Researchers Develop Liquid Biopsy for Retinoblastoma Findings by investigators at the Vision Center of Children’s Hospital Los Angeles and the University of Southern California Roski Eye Institute provide proof of concept for a safe and effective way to derive genetic information... And More...

Assessing Subclinical Neovascularization in Nonexudative AMD Via SS-OCTA

Researchers used swept-source optical coherence tomography angiography to determine the prevalence, incidence and natural history of subclinical macular neovascularization in eyes with nonexudative age-related macular degeneration, as part of a prospective, observational, consecutive case series.

Participants included those with intermediate AMD or geographic atrophy secondary to nonexudative AMD in one eye and exudative AMD in the fellow eye. All individuals were imaged using the 3×3 mm and 6×6 mm SS-OCTA fields of view (PLEX Elite 9000, Carl Zeiss Meditec). The en face slab helped detection of the MNV extended from the outer retina to the choriocapillaris. Researchers removed projection artifacts using a proprietary algorithm.

Main outcome measures included the prevalence of subclinical MNV and time to exudation with Kaplan-Meier cumulative estimates of exudation at one year.

From August 2014 through March 2017, 160 individuals underwent SS-OCTA (110 eyes with iAMD and 50 eyes with GA). SS-OCTA helped identify subclinical MNV at the time of first imaging in 23 of 160 eyes for a prevalence of 14.4 percent. Six eyes demonstrated subclinical MNV during the follow-up. Of 134 eyes with follow-up visits, a total of 13 eyes demonstrated exudation, and of these, 10 were found to have pre-existing subclinical MNV. By 12 months, the Kaplan-Meier cumulative incidence of exudation for all 134 eyes was 6.8 percent. For eyes with subclinical MNV at the time of first SS-OCTA imaging, the incidence was 21.1 percent, and for eyes without subclinical MNV, the incidence was 3.6 percent. There was no difference in the cumulative incidence of exudation from pre-existing MNV in eyes with iAMD or GA (p=0.847, log-rank test). After the detection of subclinical MNV, the risk of exudation was 15.2 times (CI, 4.2 to 55.4) greater compared with eyes without subclinical MNV.

Researchers found that, by 12 months, exudation risk was greater for eyes with documented subclinical MNV than eyes without detectable MNV. For eyes with subclinical MNV, they recommended more frequent follow-up and home monitoring; however, they couldn’t recommend intravitreal therapy until prospective studies were performed.

Source: de Oliveira Dias JR, Zhang Q, Garcia JMB, et al. Natural history of subclinical neovascularization in nonexudative age-related macular degeneration using swept-source OCT angiography. Ophthalmology 2017; Sep 27. [Epub ahead of print].

Correlation of Anti-VEGF-treated Type 3 Neovascularization in AMD

Researchers sought to correlate histologic results with previously recorded multimodal imaging results from a deceased individual with type 3 neovascularization secondary to age-related macular degeneration, as part of a case study involving an 86-year-old white woman with type 3 neovascularization secondary to AMD treated with six intravitreal injections of bevacizumab.

Multimodal retinal imaging at each clinic visit was correlated with ex vivo and high-resolution histologic images of the preserved donor eye. Clinical imaging included serial, near-infrared reflectance and eye-tracked spectral-domain optical coherence tomography. Eye tracking, applied to the donor eye, enabled identification of histologic features corresponding to clinical OCT signatures.

Main outcome measures included histologic correlates for clinical OCT signatures including: reflectivity of the vascular complex; intraretinal hyperreflective foci and intraretinal cellularity; analysis of pathologic feature topography; and evaluation of the subretinal pigment epithelium plus basal lamina space.

Clinical imaging showed a deep neovascular lesion closely related to a mixed serous and drusenoid pigment epithelium detachment, characteristic of type 3 neovascularization. Antiangiogenic therapy achieved a complete resolution of exudation. The PED progressively flattened with each treatment, leaving a persistent triangular hyperreflectivity in the outer retina. This deep lesion histologically correlated with a vascular complex implanted into sub-RPE basal laminar deposits.

Researchers observed no relationship between the choriocapillaris and sub-RPE plus BL space, and found that both RPE-derived and lipid-filled cells correlated with clinical intraretinal hyperreflective foci. They added that the sub-RPE plus BL space contained macrophages, lymphocytes, Müller cell processes and subducted RPE.

Source: Li M, Dolz-Marco R, Messinger, JD, et al. Clinicopathologic correlation of anti-vascular endothelial growth factor-treated type 3 neovascularization in age-related macular degeneration. Ophthalmology 2017; Sep 27. [Epub ahead of print].

Treatment Outcomes for OCT-based Stages in Type 3 Neovascularization

Scientists compared the stages of 12-month type 3 neovascularization treatment outcomes, using optical coherence tomography. The retrospective, observational study included 40 individuals (40 eyes) newly diagnosed with type 3 neovascularization.

The individuals initially received three monthly anti-vascular endothelial growth factor injections. Repeat treatment was performed with recurrence of fluid. Scientists classified disease staging using an OCT-based method. They compared best-corrected visual acuity at diagnosis and at 12 months, and degree of change in BCVA between the different disease stages. In addition, they estimated disease progression.

A total of 14 (35 percent) individuals were classified as stage 2, and 26 (65 percent) were classified as stage 3. BCVA values at diagnosis and at 12 months were 0.61 ±0.31 (20/81 Snellen equivalents) and 0.46 ±0.30 (20/57) in stage 2 and 0.67 ±0.42 (20/93) and 0.70 ±0.49 (20/100) in stage 3 groups, respectively. Scientists found a significant difference in BCVA change between the two groups (p=0.036). During follow-up, three retinal pigment epithelium tears and two submacular hemorrhages developed in the stage 3 group. Scientists noted disease progression from stage 2 to stage 3 in two individuals (14.3 percent).

Scientists found that visual outcomes were worse in stage 3 than in stage 2, and adverse events that might lead to abrupt visual deterioration developed only in stage 3. They suggested that further studies were needed to reveal whether anti-VEGF therapy could suppress progression of the disease stages.

SOURCE: Kim JH, Chang YS, Kim JW, et al. Difference in treatment outcomes according to optical coherence tomography-based stages in type 3 neovascularization (retinal angiomatous proliferation). Retina 2017; Oct. 10. [Epub ahead of print].

RPE Tears After Anti-VEGF Therapy for nAMD

Researchers looked at retinal pigment epithelium tears, their treatment patterns and long-term visual outcomes in individuals with neovascular age-related macular degeneration, as part of a case-control analysis from an observational database. They identified treatment-naïve eyes enrolled in the Fight Retina Blindness! observational study assessing anti-vascular endothelial growth factor treatment for nAMD between January 2006 and January 2017. Cases were defined as eyes in which an RPE tear developed during treatment. Three control eyes per case were matched for age, baseline visual acuity, lesion size, treatment duration before tearing, and duration of follow-up.

Researchers classified cases as having early or late tears using a segmented regression model, and compared baseline characteristics between the two groups. They evaluated VA and injections received in tear eyes and controls at baseline, before and immediately after the tear, and 12 and 24 months later. They also assessed VA at several visits within each group. Main outcome measures included VA, time to tear and injections received.

The study included 55 cases and 165 matched control eyes. Segmented regression estimated a breakpoint for time to tear at 182 days. Researchers defined eyes as having early tears if they tore before the breakpoint (38/55 eyes [69 percent]) and as late tears if they tore afterward (17/55 eyes [31 percent]). Baseline VA was significantly lower in early compared with late tears (53.6 vs. 63.4 letters; p=0.009). VA improved in early tears before the tear (+5.6 letters from baseline; p=0.01), decreased immediately after the tear (-8.3 letters; p=0.002), then recovered with no difference compared with control eyes 12 and 24 months later (p>0.05 for both). Late tear eyes had significantly lower VA than controls before tearing (55.5 vs. 66.9 letters; p<0.001). VA didn’t decrease significantly after tears, but continued to decline compared with controls at all endpoints. Both early and late tear eyes received more injections after tearing than controls.

Researchers concluded that RPE tears acted differently depending on when they occurred. Furthermore, they wrote, long-term visual outcomes in eyes affected by RPE tearing might be related more to the individual's response to therapy than to the tear itself.

SOURCE: Invernizzi A, Nguyen V, Arnold J, et al. Early and late retinal pigment epithelium tears after anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration. Ophthalmology 2017; Oct 6. [Epub ahead of print].

Vitreomacular Interface Impact on TREX Regimen With Exit Strategy in nAMD

Researchers evaluated the impact of a vitreomacular interface in a treat-and-extend regimen with an exit strategy, in individuals with neovascular age-related macular degeneration, as part of a retrospective cohort study. Participants included 593 eyes of 498 individuals with nAMD.

Eyes were treated according to a TREX regimen with an exit criterion, defined as no signs of disease activity during three consecutive, 16-week injection visits. Researchers evaluated the impact of the VMI and presence of an epiretinal membrane assessed by spectral-domain OCT based on certain parameters.

Main outcome measures included the effect of vitreomacular adhesion and ERM on the mean treatment interval, number of injections, likelihood of fulfilling the exit criterion, choroidal neovascularization recurrences, CRT decrease and BCVA improvement.

During the TREX period, posterior vitreous detachment eyes needed significantly fewer injections (mean: 10.6 ±5.9) than VMA eyes (mean: 12.6 ±6.7; p=0.0008), and the mean injection interval was shorter in VMA eyes (8.3 ±3.1 weeks) than in PVD eyes (9.5 ±3.5 weeks; p=0.0008). Eyes with PVD at baseline and without an ERM were 9.2 and 11.4 times more likely to fulfill the exit criterion than eyes with VMA and ERM (p=0.006 and p=0.004, corrected), respectively. Although CRT decreases (p=0.16) and BCVA improvements (p=0.32) didn’t differ with respect to the VMI configuration, ERM had a significant impact on the CRT decrease (ERM present: +11 ±198 μm vs. ERM absent: -92 ±136 μm; p=0.041). Vitreomacular adhesion at treatment cessation was associated significantly with disease recurrence (likelihood ratio, 7.8; p=0.013, corrected) whereas the presence of an ERM wasn’t associated with choroidal neovascularization recurrence (p=0.18).

Researchers concluded that the VMI configuration and ERM presence had a significant impact on treatment frequency, exit criterion in this TREX regimen and recurrence risk after treatment cessation. Researchers indicated that eyes with VMA should be monitored carefully for new disease activity after treatment cessation.

SOURCE: Munk MR, Arendt P, Yu S, et al. The impact of the vitreomacular interface in neovascular age-related macular degeneration in a treat-and-extend regimen with exit strategy. Ophthalmology Retina 2017; Sep 29. [Epub ahead of print].

Comparative Dosing of Ranibizumab in Bevacizumab-resistant DME: The REACT Study

Investigators assessed the efficacy of ranibizumab for persistent diabetic macular edema previously treated with bevacizumab and compared monthly vs. treat-and-extend dosing, as part of a 12-month open-label prospective, randomized, comparative dosing study. Twenty-seven participants with persistent, foveal-involving DME recently treated with bevacizumab were included.

All participants were scheduled to receive three initial monthly 0.3-mg ranibizumab injections before randomization to monthly (n=15) or TREX (n=12) injection protocols over 12 months. The treatment interval was extended by two weeks up to a maximum interval of 12 weeks in the TREX group if central subfield thickness was 300 μm or less, or if complete absence of intraretinal or subretinal fluid on the macular cube was observed. The follow-up interval was decreased by two weeks if CST increased to 300 μm or more with associated intraretinal or subretinal fluid, or both.

Main outcome measures included change in Early Treatment Diabetic Retinopathy Study best-corrected visual acuity, CST and adverse events. Before study enrollment, participants received an average of 8.6 bevacizumab injections. At month 12, mean ETDRS BCVA improved by +5.3 letters (p<0.05), and mean CST decreased by 99.6 μm (p<0.01) in all individuals. At the study exit, 18.5 percent of individuals gained three or more lines of vision, and 3.7 percent lost three or more lines. Participants treated via the TREX protocol gained 8.4 letters, and CST decreased by 120.2 μm; whereas those treated by monthly injection gained 2.7 letters, and CST decreased by 83.1 μm at month 12.

Investigators noted significant functional and anatomic improvements after conversion to ranibizumab in eyes with persistent DME refractory to bevacizumab. They added that visual and anatomic outcomes were similar in TREX and monthly treatment protocols.

SOURCE: Ehlers JP, Wang K, Singh RP, et al. A prospective randomized comparative dosing trial of ranibizumab in bevacizumab-resistant diabetic macular edema: The REACT study. Ophthalmology Retina 2017; Sep 28. [Epub ahead of print].

OCT Biomarkers as Functional Outcome Predictors in DME Treated With DEX Implant

Scientists wrote that identification and characterization of individuals with diabetic macular edema are important for individualizing treatment and optimizing outcomes. They investigated optical coherence tomography biomarkers for DME treated by intravitreal dexamethasone implants, as part of a multicenter, retrospective, observational cohort study.

Scientists included 299 eyes from 284 individuals treated with DEX implant for DME (naïve, n=209; refractory, n=90). The baseline best-corrected visual acuity was between 0.3 and 1 on a logMAR visual chart.

Scientists evaluated the OCT scans previous to DEX implants for: submacular fluid; size and location of cystoid changes; inner segment-outer segment continuity; quantity and location of hyperreflective foci; vitreomacular interface abnormalities; and epiretinal membrane. Scientists recorded the BCVA and central macular thickness at baseline, and at one, two and four months after treatment with DEX implants. They analyzed correlations between OCT measures and visual outcomes using the generalized estimating equations procedure.

Main outcome measures included the correlation between spectral-domain OCT measures at baseline and BCVA response (mean change from baseline; categorized improvement [<5, 5 to 9, or ≥10; Early Treatment Diabetic Retinopathy Study letters] in BCVA) after treatment with a DEX implant.

The presence of subretinal fluid (OR, 1.98; CI, 1.23 to 3.20; p=0.01), absence of HRF (OR, 3.66; CI, 1.40 to 9.62; p=0.01) and integrity of the IS-OS layer (OR, 2.09; CI, 1.30 to 3.37; p=0.003) were all predictive of better visual outcomes after treatment with DEX implants. Although eyes with naïve DME gained more vision than refractory eyes (p<0.001), the predictive value of OCT findings didn’t differ according to this classification.

Scientists concluded that SD-OCT was useful in identifying various imaging findings in DME. Among eyes with DME, those with submacular fluid, no HRF and a continuous IS-OS layer responded better to DEX implants than those without these features, they found. Scientists wrote that the findings call for further study of combinations of OCT and metabolic biomarkers.

Autoregulation of ONH Blood Flow During Vitreous Surgery in Individuals With Hypertension & Hyperlipidemia

Scientists examined whether hypertension and hyperlipidemia affected autoregulation of optic nerve head blood flow during vitrectomy, as part of a cohort study.

Seventeen eyes from 17 subjects with HTN and HL, and 19 eyes from 19 control subjects without systemic disorders underwent vitrectomy for treatment of epiretinal membranes or macular holes. Following standard 25-gauge microincision vitrectomy, the mean blur rate—an index of relative ONH blood flow—in the vascular area and MBR in the tissue area were measured using laser speckle flowgraphy. Measurements were conducted before, and five and 10 minutes after an approximately 15-mmHg rise in intraocular pressure. The parameters represented relative values of ONH blood flow (percent, compared to baseline). Scientists calculated the recovery rate of ONH blood flow using the equation: (MBR at 10 min. - MBR at 5 min.)/(MBR at baseline - MBR at 5 min.).

Ocular perfusion pressure in all subjects dropped five and 10 minutes after the increase in IOP. Vascular MBR in subjects with HTN and HL (75.5 ±14.8) was significantly lower than that in controls (86.7 ±12.1) 10 minutes after IOP elevation (p=0.019). The recovery rate of vascular blood flow was significantly lower in the HTN and HL groups than in the control group (p=0.002).

Scientists’ wrote that their results suggested that HTN and HL impaired autoregulation in the vascular component of ONH blood flow during vitrectomy.

SOURCE: Hashimoto R, Sugiyama T, Ubuka M, et al. Impairment of autoregulation of optic nerve head blood flow during vitreous surgery in patients with hypertension and hyperlipidemia. Graefes Arch Clin Exp Ophthalmol 2017; Sep 23. [Epub ahead of print].

Reoperation Rate RRD With Coexistent Macular Hole

Investigators examined surgical outcomes in individuals with coexistent macular hole and rhegmatogenous retinal detachment, as part of a retrospective case series. They looked at all individuals who underwent surgical repair of concomitant MH and retinal detachment in their facility between January 2014 and December 2016.

At least one retinal break was noted in all MHRD cases. Exclusion criteria included MHRD related to high myopia without peripheral retinal tears. Data collected included presence of proliferative vitreoretinopathy and classification at time of surgical repair, details of surgical repair including whether internal limiting membrane peeling was achieved, type of ILM staining used, presence of retinal detachment in the fellow eye, and duration of follow-up. Outcomes evaluated included visual acuity comparisons, reoperation rate, final anatomic success and MH closure rate.

Over the study period, MHRD cases accounted for 17 of 745 (2.3 percent) of all repaired RDs in the practice. Proliferative vitreoretinopathy was present in 53 percent of MHRD cases. Reoperation rates for MHRD were significantly higher than the practice average for all RD repairs (29 percent vs. 9.7 percent; p=0.01). Final anatomic success with RD was achieved in 100 percent of individuals. Internal limiting membrane peeling was performed in 15 of 17 individuals. The macular hole closure rate was 71 percent after initial surgery. Although 82 percent of individuals experienced equal or improved vision, only 24 percent of individuals achieved VA better than 20/80. Retinal detachment in the contralateral eye was noted in three of 16 individuals (19 percent) before initial presentation or during the follow-up period.

Investigators wrote that visual outcomes in MHRD cases were underwhelming because of high rates of PVR macula-off RRD and reoperation, and relatively low MH closure rates; as such, they suggested aggressive surgical techniques to repair MHRD.

SOURCE: Najafi M, Brown JS, Rosenberg KI, et al. Increased reoperation rate in surgical treatment of rhegmatogenous retinal detachment with coexistent macular hole. Ophthalmology Retina 2017; Sep 28. [Epub ahead of print].

Persistent Diplopia After PPV With Encircling Band for RRD

Researchers evaluated the incidence of persistent diplopia in the primary position after encircling band procedures with pars plana vitrectomy and reported the outcomes, as part of an observational, retrospective study.

Participants included 116 individuals who underwent successful rhegmatogenous retinal detachment at the researchers’ center from 2009 through 2014, including all individuals with RRD who underwent successful PPV with an encircling band. Those reporting diplopia more than two months after retinal surgery were identified and evaluated by strabismus colleagues.

The main outcome measures included near and far deviation in prism diopters, degree of anisometropia and visual acuity. Six of 116 individuals reported persistent diplopia in the primary position (5.2 percent). Diplopia most often was related to vertical microdeviations from 3 to 5 prism diopters, and it was managed adequately with prisms. The deviation remained unchanged during follow-up, except in one individual.

Researchers determined that persistent diplopia associated with PPV with an encircling band had a low incidence and a small angle of deviation, and was corrected successfully with prisms.

SOURCE: Navarrete-Sanchis J, Ortega-Evangelio L, Tomás-Torrent, et al. Persistent diplopia in primary position after pars plana vitrectomy with encircling band in rhegmatogenous retinal detachment. Ophthalmology Retina 2017; Sep 19. [Epub ahead of print].