Category: Peer-reviewed

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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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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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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Effect of scan quality on diagnostic accuracy of spectral domain optical coherence tomography in glaucoma – Accepted Manuscript

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Abstract: Purpose: To evaluate the effect of scan quality on the diagnostic accuracies of optic nerve head (ONH), retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) parameters of spectral domain optical coherence tomography (SD-OCT) in glaucoma.Design: Cross-sectional study.Methods: 252 eyes of 183 control subjects (mean MD: -1.84 dB) and 207 eyes of 159 glaucoma patients (mean MD: -7.31 dB) underwent ONH, RNFL and GCC scanning with SD-OCT. Scan quality of SD-OCT images was based on signal strength index (SSI) values. Influence of SSI on diagnostic accuracy of SD-OCT was evaluated by receiver operating characteristic (ROC) regression.Results: Diagnostic accuracies of all SD-OCT parameters were better when the SSI values were higher. This effect was statistically significant (p<0.05) for ONH and RNFL but not for GCC parameters. In mild glaucoma (MD of -5 dB), area under ROC curve (AUC) for rim area, average RNFL thickness and average GCC thickness parameters improved from 0.651, 0.678 and 0.726, at a SSI value of 30 to 0.873, 0.962 and 0.886, respectively at a SSI of 70. AUCs of the same parameters in advanced glaucoma (MD of -15 dB) improved from 0.747, 0.890 and 0.873, at a SSI value of 30 to 0.922, 0.994 and 0.959, respectively at a SSI of 70.Conclusion: Diagnostic accuracies of SD-OCT parameters in glaucoma were significantly influenced by the scan quality even when the SSI values were within the manufacturer recommended limits. These results should be considered while interpreting the SD-OCT scans for glaucoma.

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Effect of nepafenac eye drops on intraocular pressure – a randomized prospective study – Accepted Manuscript

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Abstract: Purpose: To report the effect of nepafenac (0.1%) eye drops on intraocular pressure in eyes with cataract.Design: Prospective, randomized clinical trial.Methods: Three hundred and twenty-seven patients with bilateral cataracts in an institutional setting were included. All patients had a baseline intraocular pressure (IOP) ≤21 mmHg without a history of intraocular surgery in past 3 months. One eye of each individual was randomized to the treatment group with the other eye acting as a control. Nepafenac (0.1%) eye drops were instilled 3 times a day in the eye that received treatment. Intraocular pressure (IOP) with Goldmann applanation tonometer (GAT) was measured at baseline, 4 and 8 weeks. Proportion of eyes with an IOP elevation of > 4 mmHg was the main outcome measure.Results: The mean age of the participants was 45.7±4.4 years which included 192 females and 135 males. The mean IOP at baseline in the treated and control eyes was 13.8±2.5 and 13.4±3.0 mmHg which reduced to 12.0±2.0 and 12.1±1.5 mmHg at the end of 8 weeks respectively. This reduction in IOP in both groups was significant (p<0.01). The difference between the IOP in the treated and control eyes at 8 weeks was not statistically significant (p=0.34). One eye in the treated group and 2 eyes in the control group had an IOP elevation of > 4 mmHg.Conclusion: Nepafenac eye drops do not increase the IOP. They can possibly be used as an alternative to steroid medications where steroid responsiveness is a concern.

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Comparison of Hoffer Q and Haigis Formulae for Intraocular Lens Power Calculation according to the Anterior Chamber Depth in Short Eyes – Accepted Manuscript

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Abstract: Purpose: To compare the accuracy of the Hoffer Q and Haigis formulae according to the anterior chamber depth (ACD) in cases of short axial length (AL).Design: Retrospective cross-sectional studyMethods: A total of 75 eyes from 75 patients with an AL of less than 22.0 mm implanted with an Acrysof IQ intraocular lens (IOL) were enrolled. The median absolute errors (MedAEs) predicted by the Hoffer Q and Haigis formulae were compared. The correlations between ACD and the predicted refractive error calculated using the two formulae were analyzed.Results: There were no significant differences in the MedAEs predicted by the Hoffer Q and Haigis formulae (0.40 and 0.40 D, respectively). The difference between the refractive errors predicted by the Hoffer Q and Haigis formulae increased significantly as the ACD decreased (R2=0.644, P<.001). The MedAE predicted by the Haigis formula (0.40 D) was significantly smaller than that predicted by the Hoffer Q formula (0.66 D) in eyes with an ACD of less than 2.40 mm (P=.027). There were no significant differences found between the MedAEs predicted by the Hoffer Q and Haigis formulae in eyes with an ACD of 2.40 mm or more.Conclusions: The differences between the predicted refractive errors of the Hoffer Q and Haigis formula increased as ACD decreased in short eyes. Therefore, ACD should be taken into consideration when evaluating the accuracy of the IOL power calculation formulae in short eyes.

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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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High Prevalence of Demodex brevis Infestation in Chalazia – Corrected Proof

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Purpose: To investigate the correlation between demodicosis and chalazia in patients with the latter.Design: Prospective, observational, comparative study.Methods: Forty-four adult and 47 pediatric patients with chalazia and 34 adult and 30 pediatric age- and sex-matched patients without chalazia treated at an institutional referral eye center were included. All 155 patients underwent lash sampling followed by microscopic identification and counting of Demodex mites. All 91 patients with chalazia underwent surgical removal, and among them, 74 were followed up for 18 ± 4.3 months after surgery. Statistical correlation between ocular demodicosis and chalazia and its postoperative recurrence was performed.Results: Demodicosis was significantly more prevalent in chalazia patients than in control patients as a group (69.2% vs 20.3%) and when separated into pediatric (70.2% vs 13.3%) and adult (68.2% vs 26.5%) subgroups (all P < .001). Demodicosis was associated strongly with chalazia (odds ratio, 4.39; 95% confidence interval, 2.17 to 8.87; P < .001). D. brevis was significantly more prevalent (odds ratio, 18.21; 95% confidence interval, 2.22 to 149.74; P = .01) than D. folliculorum (odds ratio, 2.82; 95% confidence interval, 1.16 to 6.84, P = .02) in patients with chalazia. Patients with demodicosis tended to demonstrate recurrence (33.3% vs 10.3%; P = .02), especially in those with D. brevis (35.1% vs 13.5%; P = .03).Conclusions: There is a high prevalence of demodicosis, especially cases of caused by D. brevis, in adult and pediatric patients with chalazia, suggesting that ocular demodicosis is a risk factor for chalazia.

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