Relationship between Intraocular Pressure Fluctuation and Visual Field Progression Rates in the United Kingdom Glaucoma Treatment Study.

PURPOSE: To investigate whether intraocular pressure (IOP) fluctuation is associated independently with the rate of visual field (VF) progression in the United Kingdom Glaucoma Treatment Study. DESIGN: Randomized, double-masked, placebo-controlled multicenter trial. PARTICIPANTS: Participants with ≥5 VFs (213 placebo, 217 treatment). METHODS: Associations between IOP metrics and VF progression rates (mean deviation [MD] and five fastest locations) were assessed with linear mixed models. Fluctuation variables were mean Pascal ocular pulse amplitude (OPA), standard deviation (SD) of diurnal Goldmann IOP (diurnal fluctuation), and SD of Goldmann IOP at all visits (long-term fluctuation). Fluctuation values were normalized for mean IOP to make them independent from the mean IOP. Correlated nonfluctuation IOP metrics (baseline, peak, mean, supine, and peak phasing IOP) were combined with principal component analysis, and principal component 1 (PC1) was included as a covariate. Interactions between covariates and time from baseline modeled the effect of the variables on VF rates. Analyses were conducted separately in the two treatment arms. MAIN OUTCOME MEASURES: Associations between IOP fluctuation metrics and rates of MD and the five fastest test locations. RESULTS: In the placebo arm, only PC1 was associated significantly with the MD rate (estimate, -0.19 dB/year [standard error (SE), 0.04 dB/year]; P < 0.001), whereas normalized IOP fluctuation metrics were not. No variable was associated significantly with MD rates in the treatment arm. For the fastest five locations in the placebo group, PC1 (estimate, -0.58 dB/year [SE, 0.16 dB/year]; P < 0.001), central corneal thickness (estimate, 0.26 dB/year [SE, 0.10 dB/year] for 10 µm thicker; P = 0.01) and normalized OPA (estimate, -3.50 dB/year [SE, 1.04 dB/year]; P = 0.001) were associated with rates of progression; normalized diurnal and long-term IOP fluctuations were not. In the treatment group, only PC1 (estimate, -0.27 dB/year [SE, 0.12 dB/year]; P = 0.028) was associated with the rates of progression. CONCLUSIONS: No evidence supports that either diurnal or long-term IOP fluctuation, as measured in clinical practice, are independent factors for glaucoma progression; other aspects of IOP, including mean IOP and peak IOP, may be more informative. Ocular pulse amplitude may be an independent factor for faster glaucoma progression. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Hypotony Failure Criteria in Glaucoma Surgical Studies and Their Influence on Surgery Success.

PURPOSE: Review hypotony failure criteria used in glaucoma surgical outcome studies and evaluate their impact on success rates. DESIGN: Systematic literature review and application of hypotony failure criteria to 2 retrospective cohorts. PARTICIPANTS: A total of 934 eyes and 1765 eyes undergoing trabeculectomy and deep sclerectomy (DS) with a median follow-up of 41.4 and 45.4 months, respectively. METHODS: Literature-based hypotony failure criteria were applied to patient cohorts. Intraocular pressure (IOP)-related success was defined as follows: (A) IOP ≤ 21 mmHg with ≥ 20% IOP reduction; (B) IOP ≤ 18 mmHg with ≥ 20% reduction; (C) IOP ≤ 15 mmHg with ≥ 25% reduction; and (D) IOP ≤ 12 mmHg with ≥ 30% reduction. Failure was defined as IOP exceeding these criteria in 2 consecutive visits > 3 months after surgery, loss of light perception, additional IOP-lowering surgery, or hypotony. Cox regression estimated failure risk for different hypotony criteria, using no hypotony as a reference. Analyses were conducted for each criterion and hypotony type (i.e., numerical [IOP threshold], clinical [clinical manifestations], and mixed [combination of numerical or clinical criteria]). MAIN OUTCOME MEASURES: Hazard ratio (HR) for failure risk. RESULTS: Of 2503 studies found, 278 were eligible, with 99 studies (35.6%) lacking hypotony failure criteria. Numerical hypotony was predominant (157 studies [56.5%]). Few studies used clinical hypotony (3 isolated [1.1%]; 19 combined with low IOP [6.8%]). Forty-nine different criteria were found, with IOP < 6 mmHg, IOP < 6 mmHg on ≥ 2 consecutive visits after 3 months, and IOP < 5 mmHg being the most common (41 [14.7%], 38 [13.7%], and 13 [4.7%] studies, respectively). In both cohorts, numerical hypotony posed the highest risk of failure (HR, 1.51-1.21 for criteria A to D; P < 0.001), followed by mixed hypotony (HR, 1.41-1.20 for criteria A to D; P < 0.001), and clinical hypotony (HR, 1.12-1.04; P < 0.001). Failure risk varied greatly with various hypotony definitions, with the HR ranging from 1.02 to 10.79 for trabeculectomy and 1.00 to 8.36 for DS. CONCLUSIONS: Hypotony failure criteria are highly heterogenous in the glaucoma literature, with few studies focusing on clinical manifestations. Numerical hypotony yields higher failure rates than clinical hypotony and can underestimate glaucoma surgery success rates. Standardizing failure criteria with an emphasis on clinically relevant hypotony manifestations is needed. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Choroidal hypertransmission width on optical coherence tomography: a prognostic biomarker in idiopathic macular hole surgery.

PURPOSE: To test the hypothesis that optical coherence tomography (OCT) choroidal hypertransmission width (CHW) is a prognostic biomarker in idiopathic macular hole (MH) surgery METHODS: Retrospective cohort study of consecutive patients undergoing successful pars plana vitrectomy for idiopathic MH. We collected demographic, clinical, and OCT variables at the preoperative and last available visits. Two investigators assessed the following OCT parameters: MH minimum diameter, base diameter, CHW, ellipsoid zone, and external limiting membrane status (absent vs. present). Delta CHW was calculated as the difference between CHW and MH minimum diameter. Linear models were used to investigate factors associated with postoperative best-corrected visual acuity (BCVA) and BCVA change. RESULTS: Thirty-six eyes (36 patients) with a median (interquartile range (IQR)) follow-up of 9 (8-11) months were included. The median BCVA (IQR) improved from 0.75 (1-0.6) logMAR preoperatively to 0.2 (0.6-0.1) logMAR at the last visit (p < 0.001). Preoperative MH minimum diameter (for a 10-µm increase, estimate (standard error (SE)): 0.009 (0.003) logMAR, p = 0.003), base diameter (for a 10-µm increase, 0.003 (0.001) logMAR, p = 0.032), CHW (for a 10-µm increase, 0.008 (0.002) logMAR, p < 0.001), and delta CHW (for a 10-µm increase, 0.013 (0.005) logMAR, p = 0.009) were significantly associated with postoperative BCVA. The proportion of variance explained was the highest for MH CHW (R2 0.35), followed by minimum MH diameter (R2 0.24), delta CHW (R2 0.19), and MH base diameter (R2 0.14). None of the study variables was associated with delta BCVA. CONCLUSION: Preoperative CHW is associated with postoperative visual acuity in patients undergoing successful idiopathic MH surgery and may be a useful OCT prognostic biomarker.

RISK FACTORS OF VISION LOSS AND MULTIPLE RECURRENCES IN MYOPIC MACULAR NEOVASCULARIZATION.

PURPOSE: To investigate the factors associated with maximum visual improvement (peak vision) gain and the risk factors of peak vision loss and multiple recurrences in myopic macular neovascularization undergoing antivascular endothelial growth factor therapy. METHODS: Retrospective study of 310 eyes with active myopic macular neovascularization and median follow-up of 3.5 years. We defined peak vision gain as the maximum best-corrected visual acuity value reached under treatment and peak vision loss as best-corrected visual acuity never scoring as peak vision. We used multiple-event Prentice, Williams, and Peterson models to compute recurrences' incidence and Cox regression to identify risk factors for peak vision gain, peak vision loss, and multiple recurrences. RESULTS: Eyes with worse baseline best-corrected visual acuity {hazard ratio (HR) = 2.59 (95% confidence interval [CI]: 1.63-4.11) for 0.1 logMAR increase, P < 0.001} had higher chance to achieve peak vision. Peak vision was lost in 162 eyes (52%). Older age (HR = 1.22 [95% CI: 1.02-1.43] for 10-year increase, P = 0.02) and recurrences (HR = 1.10 [95% CI: 1.01-1.22] for event, P = 0.04) predicted nonsustained peak vision. Older age (HR = 1.13 [95% CI: 1.04-1.27] for 10-year increase, P = 0.006), larger myopic macular neovascularization (HR = 1.06 [95% CI: 1.01-1.13] for 1-mm 2 increase, P = 0.04), and juxtafoveal location (HR = 1.88 [95% CI: 1.28-2.77] vs. extrafoveal, P = 0.001) predicted multiple recurrences. CONCLUSION: Myopic macular neovascularization eyes lose vision mainly because of multiple recurrences. Patients at risk for recurrences should undergo more attentive monitoring to avoid vision loss.

Associations and Prognostic Significance of Fluctuations in Diabetic Retinopathy Severity in Eyes Treated for Diabetic Macular Edema.

INTRODUCTION: The aim of our study was to investigate factors associated with diabetic retinopathy (DR) severity fluctuations in patients undergoing intravitreal injections for diabetic macular edema and to explore risk factors for proliferative DR (PDR). METHODS: We graded ultra-widefield fundus photography imaging at each visit using the Early Treatment Diabetic Retinopathy Study Severity Scale (DRSS). We calculated the deviation from the mode (DM) of DRSS values as a proxy of DR severity fluctuations, and we analyzed its clinical associations with linear models. We computed risk factors for PDR with Cox hazard models. We included the DRSS area-under-the-curve (AUC) of DRSS scores as a covariate in all analyses. RESULTS: We included 111 eyes with a median follow-up of 44 months. Higher DRSS-AUC values (ß = +0.03 DRSS DM for unitary DRSS/month increase, p = 0.01) and a higher number of anti-VEGF injections (ß = +0.07 DRSS DM for injection, p = 0.045) were associated with wider DR severity fluctuations. Higher DRSS-AUC values (HR = 1.45 for unitary DRSS/month increase, p = 0.001) and wider DR severity fluctuations (HR = 22.35 4th quartile vs. 1st-3rd quartile of DRSS DM, p = 0.01) were risk factors for PDR. CONCLUSION: Patients with larger DR variability in response to intravitreal injections may be at higher risk of DR progression. We advocate attentive follow-up in these patients to recognize PDR early.

ASSOCIATED FACTORS AND SURGICAL OUTCOMES OF MICROCYSTOID MACULAR EDEMA AND CONE BOUQUET ABNORMALITIES IN EYES WITH EPIRETINAL MEMBRANE.

PURPOSE: To investigate the associated features and the surgical outcomes in eyes with microcystoid macular edema (MME) and cone bouquet abnormalities (CBA) undergoing epiretinal membrane peeling. METHODS: Retrospective study including patients who underwent pars plana vitrectomy for idiopathic epiretinal membrane. Factors associated with MME and CBA at baseline and their regression were identified with logistic regression models. Postoperative visual acuity was evaluated with linear mixed models from baseline to 12 months. Risk factors for new or worsened macular edema were explored with a Cox regression model. RESULTS: One hundred and eighty-seven eyes are included in this study; 30 eyes (16%) had MME and 53 eyes (28%) had CBA preoperatively. Microcystoid macular edema was associated with severe epiretinal membrane stage (odds ratio [95% confidence interval] = 3.6 [1.3-12.7], P = 0.02); CBA was inversely associated with ectopic inner foveal layer thickness (odds ratio [95% confidence interval] = 0.97 [0.97-0.99] for each 1- µ m EIFL increase, P = 0.006). Eyes with MME had worse visual acuity after epiretinal membrane peeling ( P = 0.01) and were at risk of macular edema worsening (hazard ratio [95% confidence interval] = 2.22 [1.01-5.16], P = 0.04). Older age was associated with MME persistence (odds ratio [95% confidence interval] = 2.46 [1.06-6.82] for each 10-year increase, P = 0.04). No significant associations were found for CBA. CONCLUSION: Although CBA had no prognostic consequences, MME was associated with suboptimal visual recovery and less efficient control of inflammation after surgery. Degeneration of Müller cells may have an alleged role, and further imaging and functional tests are warranted.

CLINICAL ASSOCIATIONS AND PROGNOSTIC IMPLICATIONS OF REPAIR TISSUE PROLIFERATION IN EYES WITH RETINAL PIGMENT EPITHELIUM TEARS.

PURPOSE: To investigate demographic and clinical factors influencing the longitudinal changes of retinal pigment epithelium (RPE) dehiscence area after RPE tears, including the presence of RPE tear-associated repair proliferation (TARP), and identify factors associated with TARP development over follow-up. METHODS: Retrospective, single-center, observational cohort study of patients with a history of macular neovascularization and RPE tear. The area of RPE dehiscence was measured on repeated short-wavelength fundus autofluorescence imaging. Associations between covariates and RPE dehiscence areas were tested with multivariable linear mixed models. Associations between TARP development and clinical variables were investigated with Cox regression models. Factors associated with visual acuity changing rates were explored with linear mixed models. RESULTS: Thirty-seven eyes of 36 patients were included in this study and followed for a median time of 18 months. Tear-associated repair proliferation was identified in 27 eyes (73%). The median time for TARP detection was 112 days; none of the investigated factors was significantly associated with TARP occurrence. The presence of TARP (estimate: -0.042 mm2/month; P = 0.001) and female gender (estimate: -0.035 mm2/month; P = 0.006) were associated with slower rates of RPE dehiscence enlargement over time. Faster rates of visual improvement were observed in eyes with TARP compared with those without TARP (estimate = -0.010 logarithm of the minimum angle of resolution/month if TARP was present; P = 0.008). CONCLUSION: Retinal pigment epithelium tear repair with TARP and female gender were associated with slower RPE degeneration after RPE tears. The presence of TARP was associated better visual prognosis. Additional research on factors promoting TARP development may have therapeutic and prognostic implications.

Forecasting the COVID-19 Epidemic by Integrating Symptom Search Behavior Into Predictive Models: Infoveillance Study.

BACKGROUND: Previous studies have suggested associations between trends of web searches and COVID-19 traditional metrics. It remains unclear whether models incorporating trends of digital searches lead to better predictions. OBJECTIVE: The aim of this study is to investigate the relationship between Google Trends searches of symptoms associated with COVID-19 and confirmed COVID-19 cases and deaths. We aim to develop predictive models to forecast the COVID-19 epidemic based on a combination of Google Trends searches of symptoms and conventional COVID-19 metrics. METHODS: An open-access web application was developed to evaluate Google Trends and traditional COVID-19 metrics via an interactive framework based on principal component analysis (PCA) and time series modeling. The application facilitates the analysis of symptom search behavior associated with COVID-19 disease in 188 countries. In this study, we selected the data of nine countries as case studies to represent all continents. PCA was used to perform data dimensionality reduction, and three different time series models (error, trend, seasonality; autoregressive integrated moving average; and feed-forward neural network autoregression) were used to predict COVID-19 metrics in the upcoming 14 days. The models were compared in terms of prediction ability using the root mean square error (RMSE) of the first principal component (PC1). The predictive abilities of models generated with both Google Trends data and conventional COVID-19 metrics were compared with those fitted with conventional COVID-19 metrics only. RESULTS: The degree of correlation and the best time lag varied as a function of the selected country and topic searched; in general, the optimal time lag was within 15 days. Overall, predictions of PC1 based on both search terms and COVID-19 traditional metrics performed better than those not including Google searches (median 1.56, IQR 0.90-2.49 versus median 1.87, IQR 1.09-2.95, respectively), but the improvement in prediction varied as a function of the selected country and time frame. The best model varied as a function of country, time range, and period of time selected. Models based on a 7-day moving average led to considerably smaller RMSE values as opposed to those calculated with raw data (median 0.90, IQR 0.50-1.53 versus median 2.27, IQR 1.62-3.74, respectively). CONCLUSIONS: The inclusion of digital online searches in statistical models may improve the nowcasting and forecasting of the COVID-19 epidemic and could be used as one of the surveillance systems of COVID-19 disease. We provide a free web application operating with nearly real-time data that anyone can use to make predictions of outbreaks, improve estimates of the dynamics of ongoing epidemics, and predict future or rebound waves.

Longitudinal Macular Structure-Function Relationships in Glaucoma.

PURPOSE: To investigate the relationship between longitudinal changes in macular thickness measurements from OCT and changes in central visual field (VF) in patients with glaucoma with central or advanced damage at baseline. DESIGN: Longitudinal cohort study. PARTICIPANTS: A total of 116 eyes with ≥3 years of follow-up and ≥5 macular OCT images and central 10° VF tests were selected. METHODS: OCT superpixels and VF locations were matched correcting for retinal ganglion cell (RGC) displacement. Superpixel thickness and VF total deviation (TD) values, in both logarithmic and linear scales, were averaged within 3 eccentricities (3.4°, 5.6°, and 6.8°) and superior and inferior hemiretinas and hemifields. We estimated pointwise TD rates of change and rates of change at superpixels for full macular thickness (FMT), ganglion cell complex (GCC), ganglion cell inner plexiform layer (GCIPL), and ganglion cell layer (GCL). Correlation of structure-function (SF) rates of change was investigated with parametric tests. We compared the proportion of worsening and positive slopes for superpixels and VF test locations (negative vs. positive rates of change with P < 0.05) throughout the follow-up period. Permutation analyses were used to control specificity. MAIN OUTCOME MEASURES: Magnitude of correlation between structural and functional rates of change and proportion of worsening and positive slopes as a function of follow-up time. RESULTS: The median (interquartile range) follow-up and number of exams were 4.2 (3.7-4.6) years and 8 (7-9), respectively. The highest correlation of change rates was observed at 3.4° and 5.6° eccentricities (r = 0.24, 0.41, 0.40, and 0.40 for FMT, GCC, GCIPL, and GCL for 3.4° eccentricity and r = 0.28, 0.32, 0.31, and 0.32 for FMT, GCC, GCIPL, and GCL for 5.6° eccentricity, respectively). Although GCC measures demonstrated the highest overall longitudinal SF correlations, the differences were not statistically significant. Significant structural worsening was more frequently detected than functional deterioration at 3- and 5-year time points (P < 0.025). Permutation analyses also confirmed this finding. CONCLUSIONS: Correlations between central structural and functional rates of change were weak to fair in this cohort. Structural changes were detected more frequently than functional changes. Measurements of both structure and function are required for optimal detection of central progression.

Predictors of Long-Term Visual Field Fluctuation in Glaucoma Patients.

PURPOSE: To identify predictive factors for visual field (VF) fluctuation in glaucoma patients. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 1392 eyes (816 patients) with 6 or more VFs and 3 years or more of follow-up. METHODS: For each eye, the VF mean deviation (MD) and the pointwise sensitivities were regressed against time to model the series trend, and the root mean square error (RMSE) was estimated as a measure of variability. Potential predictors were selected with least absolute shrinkage and selection operator regression and included eye laterality, ethnicity, glaucoma type, intraocular pressure (IOP) fluctuation, baseline best corrected-visual acuity, intervening cataract or glaucoma surgery, length of follow-up, frequency of testing, baseline MD, rates of VF progression, and median false positive (FP) and false negative (FN) responses. MAIN OUTCOME MEASURES: Predictors of global and pointwise VF long-term fluctuation. RESULTS: In the global model, left eye (0.063 dB; P = 0.022), Asian descent (0.265 dB; P = 0.006), larger IOP fluctuation (0.051 dB; P < 0.001), intervening cataract surgery (0.090 dB; P = 0.023), longer follow-up (0.130 dB; P < 0.001), worse baseline MD (-0.145 dB; P < 0.001), faster VF decay rate (-0.090 dB; P < 0.001), and higher FP rate (0.145 dB; P < 0.001) and FN rate (0.220 dB; P < 0.001) were predictors of VF fluctuation. In the pointwise model, larger IOP fluctuation (0.039 dB; P = 0.022), longer follow-up (0.340 dB; P < 0.001), higher VF frequency (0.238 dB; P = 0.002), intervening glaucoma surgery (0.190 dB; P = 0.01), worse baseline MD (-0.535 dB; P < 0.001), faster VF decay rate (-0.340 dB; P < 0.001), and higher FP rate (0.255 dB; P < 0.001) and FN rate (0.395 dB; P < 0.001) were associated with increased fluctuation. The multivariable model explained 57% and 28% of the pointwise and global variances, respectively. CONCLUSIONS: This study identified novel predictors of VF fluctuation, and explains nearly 60% of the pointwise variance. In the presence of factors predictive of high fluctuation, increased frequency of testing and better analytics will help to identify VF progression more accurately.

SWEPT-SOURCE AND SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY VERSUS DYE ANGIOGRAPHY IN THE MEASUREMENT OF TYPE 1 NEOVASCULARIZATION.

PURPOSE: To compare the area of Type 1 neovascularization in patients with age-related macular degeneration calculated on spectral domain optical coherence tomography angiography (SD-OCTA), swept-source OCTA, and indocyanine green angiography (ICGA). METHODS: Cross-sectional study enrolling patients with neovascular age-related macular degeneration with Type 1 neovascularization. During the same visit, ICGA (Spectralis HRA, Heidelberg, Germany), 3 × 3-mm or 6 × 6-mm SD-OCTA (CIRRUS AngioPlex model 5000; Carl Zeiss Meditec, Inc, Dublin, OH), and 3 × 3-mm or 6 × 6-mm swept-source OCTA (Plex Elite 9000; Carl Zeiss Meditec, Inc) were performed. Neovascularization areas were compared among the three instruments. The degree of consistency between measurements was investigated through the two-way mixed intraclass correlation, whereas the intermethod agreement was expressed by the Bland-Altman analysis. Mean difference and 95% confidence intervals are provided. RESULTS: Eighteen eyes of 14 white patients (10 females, 83.3%) were included in the study. The neovascularization area measured on ICGA was higher compared to that measured on both SD-OCTA (P = 0.008) and swept-source OCTA (P = 0.008), whereas no differences were found between the two OCTA. Similar results were achieved analyzing 3 × 3-mm and 6 × 6-mm scan separately. Lowest reliability resulted from the ICGA versus SD-OCTA pair (intraclass correlation = 0.786, confidence interval = 0.500-0.915). Spectral domain OCTA and swept-source OCTA exhibited an excellent agreement (mean difference = 0.2). Swept-source OCTA offered qualitatively better images of the neovascularization, compared with SD-OCTA. CONCLUSION: Better visualization of the extent of neovascularization is obtained using SS-OCT or SD-OCT compared with ICGA, which may be influenced by choroidal permeability and dye leakage. Neovascularization area on OCTA may become an objective parameter in the follow-up of age-related macular degeneration patients, along with traditional imaging techniques.

RETINAL ARTERIAL DILATION IS IMPAIRED IN EYES WITH DRUSEN AND RETICULAR PSEUDODRUSEN.

PURPOSE: To analyze static characteristics and dynamic functionality of retinal vessels in eyes with drusen and reticular pseudodrusen (RPD) using dynamic vessel analyzer. METHODS: Patients with clinical diagnosis of isolated RPD or medium-large drusen and healthy controls were enrolled in the study between July 2016 and May 2018. Participants underwent complete ophthalmologic examination, including enhanced depth imaging structural optical coherence tomography, dynamic retinal vessel analysis, and static retinal vessel analysis. RESULTS: Twenty-eight eyes of 23 patients with drusen (9 men, mean age 77 ± 6 years), 22 eyes of 16 patients with RPD (7 men, mean age: 76 ± 6 years), and 22 eyes of 22 control subjects (11 men, mean age of 75 ± 6 years) were enrolled. Static retinal vessel analysis did not show any significant difference between the three groups for the central retinal artery equivalent (P = 0.11), the central retinal vein equivalent (P = 0.27), and the arteriovenous ratio (P = 0.30). Dynamic vessel analysis showed significantly reduced arterial dilation in eyes with drusen (P = 0.0001) and RPD (P = 0.015) compared with control subjects. No significant difference was seen between drusen and RPD groups (P = 0.32). Dynamic vessel analysis of retinal veins showed no differences between the three groups (P = 0.10). CONCLUSION: Dynamic vessel analysis in eyes with drusen and RPD revealed an impaired retinal arterial dilation in response to flicker light stimulation, which further supports the relationship between cardiovascular risk and age-related macular degeneration.

Comparison of two popular nuclear disassembly techniques for cataract surgeons in training: divide and conquer versus stop and chop.

PURPOSE: To compare two common phacoemulsification techniques in the learning curve phase, and their effect on ultrasound energy dissipation. METHODS: One hundred and ten consecutive patients scheduled for cataract surgery with the same surgeon in training were prospectively enrolled. Study was divided in two parts. In the first one, 60 patients were stratified for cataract grade [nuclear opalescence (NO) grade 2-4] and divided in two groups receiving surgery with the divide-and-conquer technique (Group-1) and with the stop-and-chop technique (Group-2). In the second part, 50 patients were stratified according to cataract grade (NO2-6), and the surgeon had to choose one of the two techniques according to personal preference. The primary outcome was the cumulative dissipated energy (CDE). RESULTS: Significant differences of CDE were observed between the NO3 and NO4 cataracts in Group-1. In Group-2, this difference was not significant, suggesting that with more advanced cataracts, the stop-and-chop technique allows less ultrasound use. In the second part of the study, the stop and chop was most frequently used for more advanced cataracts. When considering harder cataracts (NO5-NO6), patients receiving surgery with the divide-and-conquer technique had higher CDE values compared to stop and chop. CONCLUSIONS: Both divide-and-conquer and stop-and-chop techniques are efficient in the learning curve. Stop and chop dissipates less energy in harder nuclei. Once surgeons reach sufficient experience with both techniques, they should switch to a stop-and-chop technique, allowing lower levels of ultrasound energy.

Reduced vascular perfusion density in idiopathic epiretinal membrane compared to macular pseudohole.

PURPOSE: To investigate the retinal capillary perfusion density by means of optical coherence tomography angiography (OCT-A) in idiopathic epiretinal membrane (ERM) and macular pseudoholes (MPH). METHODS: This observational cross-sectional study examined consecutive patients affected by ERM and MPH presenting between June 2017 and December 2017, as well as the 30 eyes of 30 healthy subjects. All patients underwent swept-source OCT-A examination. For each patient, vessel perfusion density and foveal avascular zone (FAZ) area were measured. RESULTS: Twenty-five eyes of 20 patients with ERM and 28 eyes of 24 patients with MPH were enrolled. Thirty eyes of 30 age-matched healthy controls were included. The perfusion density in the superficial capillary plexus (SCP) of ERM (0.401 ± 0.012) turned out to be inferior that MPH (0.419 ± 0.018) and controls (0.415 ± 0.017) (p < 0.01), while no significant differences were evident among the three subgroups in the deep capillary plexus (DCP) (p = 0.1). The FAZ area in the SCP was smaller in the ERM group (0.168 ± 0.123 mm2), respectively, than MPH (0.295 ± 0.013 mm2) and controls (0.213 ± 0.107 mm2) (p < 0.01), otherwise no difference were noted in the DCP (p = 0.14). CONCLUSIONS: OCT-A morphological features differ between idiopathic ERM and MPH, showing lower perfusion density in idiopathic ERM compared to MPH.

Laser photocoagulation as treatment of non-exudative age-related macular degeneration: state-of-the-art and future perspectives.

PURPOSE: To give an updated review of laser approaches to non-exudative age-related macular degeneration (AMD). METHODS: PubMed and Medline database searches were carried out using the terms "laser" and "photocoagulation" associated with "age-related macular degeneration", and latest publications up to May 2017 have been reviewed. Moreover, the design of an ongoing single-center, non-randomized, phase I-II, pilot study, the PASCAL-GA trial, coordinated by F. Bandello, MD and G. Querques, MD from the IRCCS Ospedale San Raffaele, is described. RESULTS: Either standard or subthreshold laser strategies have been tried to induce regression of distinct phenotypes of AMD, as reticular pseudodrusen (RPD), nascent geographic atrophy (nGA), and drusen-associated geographic atrophy (DAGA), with heterogeneous results. The aim of the PASCAL-GA protocol is to assess if subthreshold laser can restore the retinal pigment epithelium function in eyes with RPD and nGA offering a protective effect against extensive GA. CONCLUSIONS: New-generation medical and surgical approaches, including subthreshold laser photocoagulation, may have some success in downstaging AMD.

QUANTITATIVE ANALYSIS OF OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN ADULT-ONSET FOVEOMACULAR VITELLIFORM DYSTROPHY.

PURPOSE: To quantify the foveal avascular zone area at superficial capillary plexus (SCP) and deep capillary plexus (DCP) and the global, parafoveal, and perifoveal vessel densities at SCP, DCP, and choriocapillaris using optical coherence tomography angiography in patients affected by adult-onset foveomacular vitelliform dystrophy (AOFVD). METHODS: Twenty eyes of 20 consecutive patients (10 females, 50%) with AOFVD and 20 eyes of 20 healthy controls presenting at the Department of Ophthalmology of San Raffaele Hospital, Milan, Italy were enrolled. All patients underwent a complete ophthalmic examination, including 3-mm × 3-mm optical coherence tomography angiography centered on the macula. The vessel density was calculated in the three plexuses (i.e., SCP, DCP, and choriocapillaris) by mean of image binarization, and foveal avascular zone area was manually outlined at SCP and DCP with ImageJ software. RESULTS: In the SCP, patients with AOFVD disclosed a significant reduction of global (P < 0.001), parafoveal (P = 0.0017), and perifoveal (P = 0.0019) vessel density. In the DCP, parafoveal vessel density was higher in patients with AOFVD (P = 0.0026), whereas no significant difference was appreciated for both the global image (P = 0.5) and the perifoveal area (P = 0.5). Patients with AOFVD showed less dense choriocapillaris (P = 0.012) and perifoveal circle (P = 0.0152), whereas no difference was observed in the perifoveal zone (P = 0.07). Foveal avascular zone area was significantly enlarged at the DCP (P = 0.0184), but not at the SCP. CONCLUSION: Patients with AOFVD have quantitative vascular alterations in all vascular layers.

Refining Coats' disease by ultra-widefield imaging and optical coherence tomography angiography.

PURPOSE: The purpose of our study was to describe ultra-widefield (UWF) imaging and optical coherence tomography angiography (OCT-A) findings in affected and fellow eyes of patients with Coats' disease. METHODS: Consecutive patients affected by Coats' disease were prospectively recruited at the Department of Ophthalmology, San Raffaele Hospital, Milan, Italy in this cross-sectional, observational study. Patients underwent UWF color fundus photographs, UWF green autofluorescence, UWF fluorescein angiography (FA), optical coherence tomography (OCT), with 3 × 3 mm and 6 × 6 mm OCT-A scans of the macula. Images were qualitatively evaluated by two independent operators for the presence of pathology. RESULTS: Eleven patients affected by Coats' disease (eight males, mean age 17.1 ± 6.7 years). Nine and two patients had a clinical diagnosis of unilateral and bilateral disease, respectively. Five eyes had macular fibrosis. All clinically affected eyes exhibited retinal pathology at UWF imaging with the temporal sector most involved followed by the inferior, nasal, superior and macula. In all eyes with macular fibrosis, OCT-A revealed replacement of the foveal avascular zone with coarse vessels suggestive of vascularized fibrosis and flow void area in the choriocapillaris due to a masking effect; type 3 neovascularization was seen in 75% of cases. Seven out of nine clinically unaffected fellow eyes showed retinal pathology at UWF FA with the temporal quadrant most involved. CONCLUSION: We demonstrated that Coats' disease is a highly asymmetric bilateral disease and that UWF imaging is able to identify more retinal pathology than standard fundus imaging, thus guiding proper retinal photocoagulation. OCT-A allowed easy identification of type 3 neovascularization in a proportion of patients with macular fibrosis.

CLINICAL SPECTRUM OF MACULAR-FOVEAL CAPILLARIES EVALUATED WITH OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To describe macular-foveal capillaries (MFC) by means of optical coherence tomography angiography and to identify the clinical spectrum of this angiographic feature. METHODS: Patients with MFC presenting at the Medical Retina & Imaging Unit of the Department of Ophthalmology, University Vita-Salute San Raffaele in Milan were recruited. Patients underwent a complete ophthalmologic examination that included slit-lamp examination, fundus examination, measurement of best-corrected visual acuity, fundus autofluorescence, and spectral-domain optical coherence tomography (Spectralis HRA + OCT; Heidelberg Engineering, Heidelberg, Germany). Fluorescein angiography was performed in selected cases. Optical coherence tomography angiography was performed through Zeiss prototype (AngioPlex, CIRRUS HD-OCT models 5000; Carl Zeiss Meditec, Inc, Dublin, OH). RESULTS: Twelve eyes of 10 consecutive white patients (5 men and 5 women; 50%) presenting MFC were included. Mean age was 66.2 ± 10.2 years (range, 53-79 years); mean best-corrected visual acuity was 0.1 ± 0.13 logarithm of the minimum angle of resolution (range, 0-0.4 logarithm of the minimum angle of resolution, corresponding to 20/20 to 20/50). Mean central macular thickness was 348 ± 57.6 µm. Two patients were affected by macular pucker, two by postsurgical macular edema, two by age-related macular degeneration, one by diabetic retinopathy, one by dome-shaped macula, one presented with chronic serous chorioretinopathy, and one with branch artery occlusion. Six eyes disclosed a complete absence of the foveal avascular zone, whereas the six other cases showed a partial foveal avascularity. No significant difference was found between complete and incomplete MFC with regards to best-corrected visual acuity (P = 0.272) and central macular thickness (P = 0.870). CONCLUSION: Cases of persistent MFC are heterogeneous in demographic characteristics, fundus appearance, and visual function. However, MFC, presenting either as complete absence of the foveal avascular zone or only partial foveal avascularity, may complicate different retinal abnormalities or represents a coincident finding.

Importance of Light Filters in Modern Vitreoretinal Surgery: An Update of the Literature.

PURPOSE: Direct endobulbar illumination during vitreoretinal surgery causes light-induced retinal damage known as phototoxicity. Spectral filters have been proposed to eliminate hazardous wavelengths from the emission spectrum before entering the eye. The purpose of our paper is to review advances in vitreoretinal surgery, focusing on intraoperative light filters. METHODS: A PubMed and Medline database search was carried out using the terms "spectral filters" associated with "vitreoretinal surgery," "phototoxicity," and "vitrectomy." Original articles, reviews, and book chapters up to March 2017 were reviewed; a few select articles published before 2000 are included for historical purposes. Material from recent meeting presentations was also added. The preferred language for the reviewed literature was English. RESULTS: Spectral filters significantly reduce the risk of phototoxicity associated with endoillumination in vitreoretinal surgery, allowing higher exposure times than with optic light fibers alone. Spectral filters may affect intraoperative luminance, but do not alter color contrast. Amber filters showed superiority over green and yellow filters. CONCLUSION: The choice of light sources coupled to spectral filters is strongly suggested, especially in dye-assisted chromovitrectomy. Histological donor eye studies and large multicenter trials are needed to validate the amount of photoprotection provided by spectral filters before a general recommendation can be made.