Author: Ophthalmology

Author reply – Corrected Proof

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We are pleased to receive comments regarding our manuscript reporting transsynaptic retrograde degeneration (TRD) of retinal ganglion cells after infarction in various areas of the brain. We measured retinal nerve fiber layer (RNFL) thickness to indire…

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Polymorphisms in Vascular Endothelial Growth Factor Receptor 2 Are Associated with Better Response Rates to Ranibizumab Treatment in Age-related Macular Degeneration – Corrected Proof

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Purpose: Intravitreal anti–vascular endothelial growth factor (VEGF) injections are currently the standard treatment for neovascular age-related macular degeneration (AMD), but a broad range of response rates has been observed. We evaluated the assoc…

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Author reply – Corrected Proof

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We thank Galvis et al for their letter. We also noted in our study that there are no differences in myopia progression when comparing myopic children with or without atropine treatment in both the intervention (recess outside classroom) and control gr…

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Clinical Pharmacokinetics of Intra-arterial Melphalan and Topotecan Combination in Patients with Retinoblastoma – Corrected Proof

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Purpose: To assess the antitumor activity, toxicity, and plasma pharmacokinetics of the combination of melphalan and topotecan for superselective ophthalmic artery infusion (SSOAI) treatment of children with retinoblastoma.Design: Single-center, prospective, clinical pharmacokinetic study.Participants: Twenty-six patients (27 eyes) with intraocular retinoblastoma.Methods: Patients with an indication for SSOAI received melphalan (3–6 mg) and topotecan (0.5–1 mg; doses calculated by age and weight). Plasma samples were obtained for pharmacokinetic studies, and a population approach via nonlinear mixed effects modeling was used. Safety and efficacy were assessed and compared with historical cohorts of patients treated with melphalan single-agent SSOAI.Main Outcome Measures: Melphalan and topotecan pharmacokinetic parameters and efficacy and safety parameters.Results: Twenty-seven eyes from 26 consecutive patients received 66 cycles of SSOAI melphalan and topotecan in combination. All 5 eyes treated as primary therapy responded to the combination chemotherapy and were preserved. Sixteen of the 22 eyes with relapsed or resistant tumors responded, but 3 of them ultimately underwent enucleation at a median of 8 months (range, 7.9–9.1 months). The incidence of grade III and IV neutropenia was 10.6% and 1.5%, respectively, which was comparable with historical controls of single-agent SSOAI melphalan. No episode of fever neutropenia was observed, and no patient required transfusion of blood products. The large variability in melphalan pharmacokinetics was explained by body weight (P < 0.05). Concomitant topotecan administration did not influence melphalan pharmacokinetic parameters. There was no effect of the sequence of melphalan and topotecan administration in plasma pharmacokinetics.Conclusions: A regimen combining melphalan and topotecan for SSOAI treatment of retinoblastoma is active and well tolerated. This combination chemotherapy previously showed synergistic pharmacologic activity, and we herein provide evidence of not increasing the hematologic toxicity compared with single-agent melphalan.

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Intravitreal Anti–Vascular Endothelial Growth Factor for Submacular Hemorrhage from Choroidal Neovascularization – Corrected Proof

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Purpose: To evaluate the efficacy of intravitreal anti–vascular endothelial growth factor (VEGF) monotherapy for patients diagnosed with exudative age-related macular degeneration (AMD) accompanied by submacular hemorrhage.Design: Retrospective, observational case series.Participants: Ninety-one eyes of 91 patients who initially presented with submacular hemorrhage associated with exudative AMD from October 2009 to September 2012. Patients were followed up for at least 6 months after treatment.Methods: Best-corrected visual acuity (BCVA) was measured at diagnosis and at 1, 3, and 6 months after treatment. The duration of symptoms was estimated. The extent of hemorrhage was estimated using fundus photography, and central foveal thickness was measured using optical coherence tomography. Change in BCVA during 6 months after treatment was estimated. The correlation of BCVA at 6 months with duration of symptoms, extent of hemorrhage, and central foveal thickness was evaluated.Main Outcome Measures: The BCVA, duration of symptoms, extent of hemorrhage, and central foveal thickness.Results: The mean duration of symptoms was 27.6±39.5 days. The mean extent of hemorrhage was 7.8±5.6 disc areas, and the mean central foveal thickness was 610.1±249.6 μm. All eyes were treated with 3.2±0.8 (range, 1–5) monthly intravitreal anti-VEGF injections during the 6-month follow-up period. The logarithm of the minimum angle of resolution BCVA at diagnosis and at 1, 3, and 6 months after the initial diagnosis was 1.38±0.53 (Snellen equivalent, 20/479), 1.27±0.57, 1.05±0.58, and 0.96±0.65 (Snellen equivalent, 20/182), respectively. The BCVA at 6 months significantly improved from baseline (P < 0.001). Poor BCVA at 6 months correlated with a longer duration of symptoms, greater extent of hemorrhage, and greater central foveal thickness (P = 0.008, P = 0.004, and P = 0.014, respectively).Conclusions: Anti-VEGF monotherapy was found to be a useful treatment option for exudative AMD accompanied by submacular hemorrhage. However, the limited efficacy in eyes with large hemorrhage may suggest the need for more aggressive treatment in these cases.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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Retinal Blood Vessel Positional Shifts and Glaucoma Progression – Corrected Proof

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Purpose: To determine the characteristics and significance of retinal blood vessel (RBV) positional shifts over time in a cohort of patients with progressive glaucoma.Design: Retrospective cohort study.Participants: Baseline and serial stereophotographs from 1 eye of 125 patients with open-angle glaucoma with ≥8 reliable Swedish interactive threshold algorithm standard visual fields (VFs) were included. On the basis of global rates of threshold sensitivity change, patients with glaucoma were divided into groups of minimal (<−0.02 decibels [dB]/year), moderate (−0.02 to −0.65 dB/year), or fast (≥−0.65 dB/year) progression. To determine whether graders’ assessments of RBV positional shifts were false-positives, a control group consisting of 33 patients with glaucoma with 2 sets of photographs taken on the same day was included.Methods: Masked graders reviewed serial photographs aligned with automated alternation flicker (EyeIC, Narbeth, PA) and assessed them for the presence of any discrete RBV positional shifts (2 graders) and for traditional measures of structural progression (2 graders), including neuroretinal rim loss, parapapillary atrophy progression, and disc hemorrhage (DH).Main Outcome Measures: Presence or absence of RBV positional shifts, rates of VF progression, and presence or absence of traditional measures of structural progression.Results: A total of 158 image sets (125 longitudinal and 33 same-day controls) from patients with glaucoma were included. Retinal blood vessel shifts were noted in 33 of 125 (26.4%) longitudinally followed glaucomatous eyes and 2 of 33 (6%) same-day control patients (P = 0.01). Agreement between graders I and II was 90.4% (kappa=0.77; P < 0.001). Eyes with RBV positional change progressed more rapidly than those without (−0.55 vs. −0.29 dB/year; 95% confidence interval [CI], 0.03–0.48); P = 0.03). Retinal blood vessel shift was present in 12.1% of minimal progressors versus 31.5% of moderate and fast progressors (P = 0.04). Rate of VF progression was statistically associated with RBV shift (odds ratio [OR], 2.2; 95% CI, 1.1–4.5; P = 0.03). Other variables significantly associated with RBV shift included neuroretinal rim loss (OR, 21.9; 95% CI, 5.7–83.6; P < 0.001) and DH (OR, 4.6; 95% CI, 1.5–15.5; P < 0.01). A multivariable model revealed that rim loss and DH, but not rate of functional change, were significantly associated with RBV shift.Conclusions: Retinal blood vessel positional shifts occurred in eyes with functionally progressive glaucoma, neuroretinal rim loss, and DH. This is a novel clinical finding that could help identify glaucoma progression or individuals at higher risk for future progression.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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CABP4 Mutations Do Not Cause Congenital Stationary Night Blindness – Corrected Proof

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I read with interest the analysis of Dutch patients diagnosed with congenital stationary night blindness (CSNB) by Bijveld et al, particularly what was written regarding patients with recessive mutations in calcium binding protein 4 (CABP4; Mendelian Inheritance in Man *608965). CABP4 encodes a protein that is specifically located in photoreceptor synaptic terminals, where it probably modulates photoreceptor calcium release. Only 3 of 101 patients diagnosed with CSNB in the authors’ series had CABP4 mutations, and all 3 patients (2 families) harbored the same homozygous mutation (c.646C>T; p.Arg216X). These 3 patients had nystagmus and low vision. Two were photophobic. All 3 had a normal fundus appearance and severe color deficiency. None complained of night blindness. All 3 were hyperopic. Such signs and symptoms, combined with their cone–rod dysfunction by electroretinography, should suggest a diagnosis of cone-rod disease rather than predominantly rod disease such as CSNB. However, because during scotopic flash stimulus there was an electronegative waveform, which is classically associated with CSNB, the 3 patients were labeled as CSNB2 (“incomplete CSNB,” with the “incomplete” referring to some rod function being present rather than completely absent). The authors recognized that these 3 patients had a distinct phenotype that was atypical for a diagnosis of CSNB2 and wondered whether studies of additional patients would confirm or refute their findings.

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Incidence of Visual Improvement in Uveitis Cases with Visual Impairment Caused by Macular Edema – Corrected Proof

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Purpose: Among cases of visually significant uveitic macular edema (ME), to estimate the incidence of visual improvement and identify predictive factors.Design: Retrospective cohort study.Participants: Eyes with uveitis, seen at 5 academic ocular inflammation centers in the United States, for which ME was documented to be currently present and the principal cause of reduced visual acuity (<20/40).Methods: Data were obtained by standardized chart review.Main Outcome Measures: Decrease of ≥0.2 base 10 logarithm of visual acuity decimal fraction-equivalent; risk factors for such visual improvement.Results: We identified 1510 eyes (of 1077 patients) with visual impairment to a level <20/40 attributed to ME. Most patients were female (67%) and white (76%), and had bilateral uveitis (82%). The estimated 6-month incidence of ≥2 lines of visual acuity improvement in affected eyes was 52% (95% confidence interval [CI], 49%–55%). Vision reduced by ME was more likely to improve by 2 lines in eyes initially with poor visual acuity (≤20/200; adjusted hazard ratio [HR] 1.5; 95% CI, 1.3–1.7), active uveitis (HR, 1.3; 95% CI, 1.1–1.5), and anterior uveitis as opposed to intermediate (HR, 1.2), posterior (HR, 1.3), or panuveitis (HR, 1.4; overall P = 0.02). During follow-up, reductions in anterior chamber or vitreous cellular activity or in vitreous haze each led to significant improvements in visual outcome (P < 0.001 for each). Conversely, snowbanking (HR, 0.7; 95% CI, 0.4–0.99), posterior synechiae (HR, 0.8; 95% CI, 0.6–0.9), and hypotony (HR, 0.2; 95% CI, 0.06–0.5) each were associated with lower incidence of visual improvement with respect to eyes lacking each of these attributes at a given visit.Conclusions: These results suggest that many, but not all, patients with ME causing low vision in a tertiary care setting will enjoy meaningful visual recovery in response to treatment. Evidence of significant ocular damage from inflammation (posterior synechiae and hypotony) portends a lower incidence of visual recovery. Better control of anterior chamber or vitreous activity is associated with a greater incidence of visual improvement, supporting an aggressive anti-inflammatory treatment approach for ME cases with active inflammation.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

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