Category: Peer-reviewed

Predicting Progression of Glaucoma from Rates of Frequency Doubling Technology Perimetry Change – Corrected Proof

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Purpose: To evaluate the ability of longitudinal frequency doubling technology (FDT) to predict the development of glaucomatous visual field loss on standard automated perimetry (SAP) in glaucoma suspects.Design: Prospective, observational cohort study.Participants: The study included 587 eyes of 367 patients with suspected glaucoma at baseline selected from the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES). These eyes had an average of 6.7±1.9 FDT tests during a mean follow-up time of 73.1±28.0 months.Methods: Glaucoma suspects had intraocular pressure (IOP) >21 mmHg or an optic disc appearance suspicious of glaucoma. All patients had normal or nonrepeatable abnormal SAP at baseline. Humphrey Matrix FDT (Carl Zeiss Meditec, Inc, Dublin, CA) testing was performed within 6 months of SAP testing. The study end point was the development of 3 consecutive abnormal SAP test results. Joint longitudinal survival models were used to evaluate the ability of rates of FDT pattern standard deviation (PSD) change to predict the development of visual field loss on SAP, adjusting for confounding variables (baseline age, mean IOP, corneal thickness, and follow-up measurements of SAP PSD).Main Outcome Measures: The R2 index was used to evaluate and compare the predictive abilities of the model containing longitudinal FDT PSD data with the model containing only baseline data.Results: Sixty-three of 587 eyes (11%) developed SAP visual field loss during follow-up. The mean rate of FDT PSD change in eyes that developed SAP visual field loss was 0.07 dB/year versus 0.02 dB/year in those that did not (P < 0.001). Baseline FDT PSD and slopes of FDT PSD change were significantly predictive of progression, with hazard ratios of 1.11 per 0.1 dB higher (95% confidence interval [CI], 1.04–1.18; P = 0.002) and 4.40 per 0.1 dB/year faster (95% CI, 1.08–17.96; P = 0.04), respectively. The longitudinal model performed significantly better than the baseline model with an R2 of 82% (95% CI, 74–89) versus 11% (95% CI, 2–24), respectively.Conclusions: Rates of FDT PSD change were highly predictive of the development of SAP visual field loss in glaucoma suspects. This finding suggests that longitudinal FDT evaluation may be useful for risk stratification of patients with suspected glaucoma.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

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Discriminant Value of Custom Ocular Response Analyzer Waveform Derivatives in Keratoconus – Corrected Proof

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Purpose: To evaluate the performance of corneal hysteresis (CH), corneal resistance factor, and 16 investigator-derived Ocular Response Analyzer (ORA) variables in distinguishing keratoconus (KC) from the nondiseased state.Design: Retrospective case series.Participants: Fifty-four eyes of 27 unaffected patients and 49 eyes of 25 KC patients from the Instituto de Olhos, Rio de Janeiro, Brazil.Methods: Sixteen candidate variables were derived from exported ORA signals to characterize putative indicators of biomechanical behavior. Area under the receiver operating characteristic curve (AUC) and the Z statistic were used to compare diagnostic performance.Main Outcome Measures: Discriminant value of standard and derived ORA variables as measured by AUC.Results: Fifteen of 16 candidate variables performed significantly better than chance (AUC, >0.5) at discriminating KC. Diagnostic performance was greatest for a custom variable related to the depth of deformation as defined by the minimum applanation signal intensity during corneal deformation (concavitymin; mean AUC ± standard error, 0.985±0.002) and a new measure incorporating the pressure-deformation relationship of the entire response cycle (hysteresis loop area, 0.967±0.002). Z statistics assessing the discriminative value of each of the top 5 variables demonstrated superiority to CH (AUC, 0.862±0.002). Concavitymin had the best overall predictive accuracy (cutoff value, 50.37; 94.9% sensitivity, 91.7% specificity, and 93.2% test accuracy), and the top 4 variables demonstrated the most consistent relationships to KC severity.Conclusions: Investigator-derived ORA variables related to the depth of deformation and the pressure-deformation relationship demonstrated very high test accuracy for detecting the presence of KC. Beyond their diagnostic value, the candidate variables described in this report provide mechanistic insight into the nature of the ORA signal and the characteristic changes in corneal dynamics associated with KC.Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

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Author reply – Corrected Proof

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Esmaeli’s request for clarification of issues regarding our study involves 11 points related to both the intra-arterial cytoreductive chemotherapy (IACC) protocol design and our analysis. First, the introductory quotation attributed to us was not a sta…

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Retinal Layer Segmentation in Patients with Multiple Sclerosis Using Spectral Domain Optical Coherence Tomography – Corrected Proof

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Purpose: To evaluate the thickness of the 10 retinal layers in the paramacular area of patients with multiple sclerosis (MS) compared with healthy subjects using the new segmentation technology of spectral domain optical coherence tomography (OCT). To examine which layer has better sensitivity for detecting neurodegeneration in patients with MS.Design: Observational, cross-sectional study.Participants: Patients with MS (n = 204) and age-matched healthy subjects (n = 138).Methods: The Spectralis OCT system (Heidelberg Engineering, Inc., Heidelberg, Germany) was used to obtain automated segmentation of all retinal layers in a parafoveal scan in 1 randomly selected eye of each participant, using the new segmentation application prototype.Main Outcome Measures: The thicknesses of 512 parafoveal points in the 10 retinal layers were obtained in each eye, and the mean thickness of each layer was calculated and compared between patients with MS and healthy subjects. The analysis was repeated, comparing patients with MS with and without previous optic neuritis. Correlation analysis was performed to evaluate the association between each retinal layer mean thickness, duration of disease, and functional disability in patients with MS. A logistic regression analysis was performed to determine which layer provided better sensitivity for detecting neurodegeneration in patients with MS.Results: All retinal layers, except the inner limiting membrane, were thinner in patients with MS compared with healthy subjects (P < 0.05). Greater effects were observed in the inner retinal layers (nerve fiber, ganglion cells, inner plexiform, and inner nuclear layers) of eyes with previous optic neuritis (P < 0.05). The retinal nerve fiber layer and ganglion cell layer thicknesses were inversely correlated with the functional disability score in patients with MS. The ganglion cell layer and inner plexiform layer thicknesses could predict axonal damage in patients with MS.Conclusions: Analysis based on the segmentation technology of the Spectralis OCT revealed retinal layer atrophy in patients with MS, especially of the inner layers. Reduction of the ganglion cell and inner plexiform layers predicted greater axonal damage in patients with MS.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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Low-Fluence Photodynamic Therapy versus Ranibizumab for Chronic Central Serous Chorioretinopathy: One-Year Results of a Randomized Trial – Corrected Proof

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Purpose: To compare the efficacy and safety between low-fluence photodynamic therapy (PDT) and the intravitreal ranibizumab in the treatment of chronic central serous chorioretinopathy (CSC).Design: Prospective, randomized, single-center, parallel-arm, controlled trial.Participants: Thirty-four eyes of 32 patients with chronic CSC with >6 months’ duration of symptoms or recurrent CSC were randomly placed into the low-fluence PDT group (n = 18) or the ranibizumab group (n = 16).Intervention: The patients underwent a single session of low-fluence PDT or 3 consecutive monthly injections of ranibizumab. Rescue treatment was available from month 3 if the subretinal fluid (SRF) persisted or recurred after primary treatment; low-fluence PDT was given to the ranibizumab group and intravitreal ranibizumab to the low-fluence PDT group.Main Outcome Measures: The primary outcome was the proportion of eyes with complete resolution of SRF without rescue treatment. Secondary outcomes included the mean changes in logarithm of the minimum angle of resolution best-corrected visual acuity (BCVA), central retinal thickness (CRT), and angiographic findings from baseline to 12 months.Results: At month 12, 16 eyes (88.9%) of the low-fluence PDT group maintained complete resolution of SRF without rescue treatment versus 2 eyes (12.5%) in the ranibizumab group (P < 0.001). Two eyes (11.1%) in the low-fluence PDT group and 11 eyes (68.8%) in the ranibizumab group met the criteria for rescue treatment (P = 0.001). In the low-fluence PDT group, the mean decrease in CRT from baseline was significantly greater than that in the ranibizumab group until month 6 (P < 0.05), but the differences became insignificant thereafter. The improvement in BCVA from baseline was superior in the low-fluence PDT group to that in the ranibizumab group, but the differences were not statistically significant except at month 3 (P = 0.025). On indocyanine green angiography, a significantly greater proportion of the low-fluence PDT group (16 eyes; 88.9%) showed a marked reduction in choroidal hyperpermeability after primary treatment than that of the ranibizumab group (0 eyes; P < 0.001). No serious adverse events related to the drugs or procedures were observed.Conclusions: This study represents the overall superiority of low-fluence PDT compared with intravitreal ranibizumab in the treatment of chronic CSC.Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

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