Non-Synonymous variants in premelanosome protein (PMEL) cause ocular pigment dispersion and pigmentary glaucoma.

Pigmentary glaucoma (PG) is a common glaucoma subtype that results from release of pigment from the iris, called pigment dispersion syndrome (PDS), and its deposition throughout the anterior chamber of the eye. Although PG has a substantial heritable component, no causative genes have yet been identified. We used whole exome sequencing of two independent pedigrees to identify two premelanosome protein (PMEL) variants associated with heritable PDS/PG. PMEL encodes a key component of the melanosome, the organelle essential for melanin synthesis, storage and transport. Targeted screening of PMEL in three independent cohorts (n = 394) identified seven additional PDS/PG-associated non-synonymous variants. Five of the nine variants exhibited defective processing of the PMEL protein. In addition, analysis of PDS/PG-associated PMEL variants expressed in HeLa cells revealed structural changes to pseudomelanosomes indicating altered amyloid fibril formation in five of the nine variants. Introduction of 11-base pair deletions to the homologous pmela in zebrafish by the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 method caused profound pigmentation defects and enlarged anterior segments in the eye, further supporting PMEL's role in ocular pigmentation and function. Taken together, these data support a model in which missense PMEL variants represent dominant negative mutations that impair the ability of PMEL to form functional amyloid fibrils. While PMEL mutations have previously been shown to cause pigmentation and ocular defects in animals, this research is the first report of mutations in PMEL causing human disease.

Trends in Glaucoma Surgeries Performed by Glaucoma Subspecialists versus Nonsubspecialists on Medicare Beneficiaries from 2008 through 2016.

PURPOSE: To characterize the use of laser and incisional glaucoma surgeries among Medicare beneficiaries from 2008 through 2016 and to compare the use of these surgeries by glaucoma subspecialists versus nonsubspecialists. DESIGN: Retrospective, observational analysis. PARTICIPANTS: Medicare beneficiaries (n = 1 468 035) undergoing ≥1 laser or incisional glaucoma surgery procedure during 2008 through 2016. METHODS: Claims data from a 20% sample of enrollees in fee-for-service Medicare throughout the United States were analyzed to identify all laser and incisional glaucoma surgeries performed from 2008 through 2016. We assessed use of traditional incisional glaucoma surgery techniques (trabeculectomy and glaucoma drainage implant [GDI] procedure) and microinvasive glaucoma surgery (MIGS). Enrollee and procedure counts were multiplied by 5 to estimate use throughout all of Medicare. Linear regression was used to compare trends in use of glaucoma surgeries between ophthalmologists who could be characterized as glaucoma subspecialists versus nonsubspecialists. MAIN OUTCOME MEASURES: Numbers of laser and incisional glaucoma surgeries performed overall and stratified by glaucoma subspecialist status. RESULTS: The number of Medicare beneficiaries undergoing any glaucoma therapeutic procedure increased by 10.6%, from 218 375 in 2008 to 241 565 in 2016. The total number of traditional incisional glaucoma surgeries decreased by 11.7%, from 37 225 to 32 885 (P = 0.02). The total number of MIGS procedures increased by 426% from 13 705 in 2012 (the first year MIGS codes were available) to 58 345 in 2016 (P = 0.001). Throughout the study period, glaucoma subspecialists performed most of the trabeculectomies (76.7% in 2008, 83.1% in 2016) and GDI procedures (77.7% in 2008, 80.6% in 2016). Many MIGS procedures were performed by nonsubspecialists. The proportions of endocyclophotocoagulations, iStent (Glaukos; San Clemente, CA) insertions, goniotomies, and canaloplasties performed by glaucoma subspecialists in 2016 were 22.0%, 25.2%, 56.9%, and 62.8%, respectively. CONCLUSIONS: From 2008 through 2016, a large shift in practice from traditional incisional glaucoma surgeries to MIGS procedures was observed. Although glaucoma subspecialists continue to perform most traditional incisional glaucoma surgeries, many MIGS procedures are performed by nonsubspecialists. These results highlight the importance of training residents in performing MIGS procedures and managing these patients perioperatively. Future studies should explore the impact of this shift in care on outcomes and costs.

Comparison of graft survival following penetrating keratoplasty and Descemet's stripping endothelial keratoplasty in eyes with a glaucoma drainage device.

PURPOSE: To compare corneal graft survival rates after penetrating keratoplasty (PK) and Descemet's stripping endothelial keratoplasty (DSEK) in patients with a glaucoma drainage device (GDD) or medically managed glaucoma. METHODS: A retrospective chart review was conducted on consecutive patients who underwent primary PK or primary DSEK. Inclusion criteria consisted of eyes with a diagnosis of glaucoma prior to corneal transplantation and a minimum of 6 months of follow-up. Graft failure was defined as an edematous cornea with failure to maintain deturgescence lasting beyond a period of 1 month of intense steroid therapy or vascularization and scarring resulting in irreversible loss of central graft clarity. Corneal graft survival was calculated using Kaplan-Meier survival analysis. Patients were divided into four groups: GDD-PK, GDD-DSEK, medical-PK and medical-DSEK. RESULTS: Fifty-six eyes of 56 patients were identified as meeting inclusion criteria. Among eyes with a GDD, there was no difference in the proportion of failures between PK grafts (48%) and DSEK grafts (50%) (p = 0.90). Failure occurred earlier in DSEK recipients compared to PK recipients, 5.82 ± 6.77 months versus 14.40 ± 7.70 months, respectively (p = 0.04). A Kaplan-Meier analysis did not identify a difference between the four groups with respect to graft failure (p = 0.52). CONCLUSION: There is no significant difference in graft survival rates between medically and surgically treated glaucoma patients for either PK or DSEK grafts. In patients with GDD, graft failure occurs earlier in DSEK compared to PK.

Retinal blood flow in glaucomatous eyes with single-hemifield damage.

PURPOSE: To examine the hypotheses that in glaucomatous eyes with single-hemifield damage, retinal blood flow (RBF) is significantly reduced in the retinal hemisphere corresponding with the abnormal visual hemifield and that there are significant associations among reduced retinal sensitivity (RS) in the abnormal hemifield, RBF, and structural measurements in the corresponding hemisphere. DESIGN: Prospective, nonrandomized, case-control study. PARTICIPANTS: Thirty eyes of 30 patients with glaucoma with visual field loss confined to a single hemifield and 27 eyes of 27 controls. METHODS: Normal and glaucomatous eyes underwent spectral-domain optical coherence tomography (SD-OCT) and standard automated perimetry. Doppler SD-OCT with a double-circle scanning pattern was used to measure RBF. The RBF was derived from the recorded Doppler frequency shift and the measured angle between the beam and the vessel. Total and hemispheric RBF, retinal nerve fiber layer (RNFL), and ganglion cell complex (GCC) values were calculated. The RS values were converted to 1/Lambert. Analysis of variance and regression analyses were performed. MAIN OUTCOME MEASURES: Total and hemispheric RS, RBF, RNFL, and GCC values. RESULTS: The total RBF (34.6±12.2 µl/minute) and venous cross-sectional area (0.039 ± 0.009 mm(2)) were reduced (P<0.001) in those with glaucoma compared with controls (46.5 ± 10.6 µl/minute; 0.052 ± 0.012 mm(2)). Mean RBF was reduced in the abnormal hemisphere compared with the opposite hemisphere (15.3 ± 5.4 vs. 19.3 ± 8.4 µl/minute; P = 0.004). The RNFL and GCC were thinner in the corresponding abnormal hemisphere compared with the opposite hemisphere (87.0 ± 20.2 vs. 103.7 ± 20.6 µm, P = 0.002; 77.6 ± 12.1 vs. 83.6 ± 10.1 µm, P = 0.04). The RBF was correlated with RNFL (r = 0.41; P = 0.02) and GCC (r = 0.43; P = 0.02) but not the RS (r = 0.31; P = 0.09) in the abnormal hemisphere. The RBF (19.3 ± 8.4 µl/minute), RNFL (103.7 ± 20.6 µm), and GCC (83.6 ± 10.1 µm) were reduced (P<0.05) in the hemisphere with apparently normal visual field in glaucomatous eyes compared with the mean hemispheric values of the normal eyes (23.2 ± 5.3 µl/minute, 124.8 ± 9.6 µm, and 96.1 ± 5.7 µm, respectively). CONCLUSIONS: In glaucomatous eyes with single-hemifield damage, the RBF is significantly reduced in the hemisphere associated with the abnormal hemifield. Reduced RBF is associated with thinner RNFL and GCC in the corresponding abnormal hemisphere. Reduced RBF and RNFL and GCC loss also are observed in the perimetrically normal hemisphere of glaucomatous eyes.

A Hybrid Deep Learning Classification of Perimetric Glaucoma Using Peripapillary Nerve Fiber Layer Reflectance and Other OCT Parameters from Three Anatomy Regions.

Précis: A hybrid deep-learning model combines NFL reflectance and other OCT parameters to improve glaucoma diagnosis. Objective: To investigate if a deep learning model could be used combine nerve fiber layer (NFL) reflectance and other OCT parameters for glaucoma diagnosis. Patients and Methods: This is a prospective observational study where of 106 normal subjects and 164 perimetric glaucoma (PG) patients. Peripapillary NFL reflectance map, NFL thickness map, optic head analysis of disc, and macular ganglion cell complex thickness were obtained using spectral domain OCT. A hybrid deep learning model combined a fully connected network (FCN) and a convolution neural network (CNN) to develop to combine those OCT maps and parameters to distinguish normal and PG eyes. Two deep learning models were compared based on whether the NFL reflectance map was used as part of the input or not. Results: The hybrid deep learning model with reflectance achieved 0.909 sensitivity at 99% specificity and 0.926 at 95%. The overall accuracy was 0.948 with 0.893 sensitivity and 1.000 specificity, and the AROC was 0.979, which is significantly better than the logistic regression models (p < 0.001). The second best model is the hybrid deep learning model w/o reflectance, which also had significantly higher AROC than logistic regression models (p < 0.001). Logistic regression with reflectance model had slightly higher AROC or sensitivity than the other logistic regression model without reflectance (p = 0.024). Conclusions: Hybrid deep learning model significantly improved the diagnostic accuracy, without or without NFL reflectance. Hybrid deep learning model, combining reflectance/NFL thickness/GCC thickness/ONH parameter, may be a practical model for glaucoma screen purposes.

Acute serous and hemorrhagic choroidal effusion associated with topical dorzolamide therapy.

Purpose: To report a case of acute onset unilateral hemorrhagic and serous choroidal effusion associated with dorzolamide administration and antiplatelet use that recurred in a patient who experienced a dorzolamide-induced choroidal effusion ten years prior to presentation. Observations: A 78-year-old male with a history of POAG in both eyes presented with sudden onset decreased vision and flashes of light in the left eye two days after escalating from timolol maleate 0.5% twice daily in both eyes to fixed combination dorzolamide-timolol 22.3-6.8 mg/mL twice daily in both eyes. Systemic medication included daily aspirin 81 mg for primary prevention of cardiovascular disease. Dilated fundus examination and B-scan ultrasound of the left eye revealed a hemorrhagic choroidal effusion in the nasal retinal periphery and low lying serous choroidal effusion in the temporal periphery. Complete resolution of the choroidal detachment was achieved in four days following prompt cessation of dorzolamide, and treatment with topical prednisolone acetate 1% four times daily and atropine 1% two times daily. Conclusions and importance: Topical dorzolamide may induce an idiosyncratic reaction leading to serous and hemorrhagic choroidal effusion, which can be exacerbated by antiplatelet use. Prompt recognition and management of drug-induced choroidal effusion can lead to improved visual outcomes and prevent long-term sequelae.

Direct Costs of Second Aqueous Shunt Implant Versus Transscleral Cyclophotocoagulation (The Assists Trial).

PRCIS: The cost of cyclophotocoagulation is less than the cost of a second glaucoma drainage device. PURPOSE: To compare the total direct costs of implantation of a second glaucoma drainage device (SGDD) with transscleral cyclophotocoagulation (CPC) for patients with inadequately controlled intraocular pressure (IOP) reduction, despite the presence of a preexisting glaucoma drainage device in the ASSISTS clinical trial. METHODS: We compared the total direct cost per patient, including the initial study procedure, medications, additional procedures, and clinic visits during the study period. The relative costs for each procedure during the 90-day global period and the entire study period were compared. The cost of the procedure, including facility fees and anesthesia costs, were determined using the 2021 Medicare fee schedule. Average wholesale prices for self-administered medications were obtained from AmerisourceBergen.com. The Wilcoxon rank sum test was used to compare costs between procedures. RESULTS: Forty-two eyes of 42 participants were randomized to SGDD (n=22) or CPC (n=20). One CPC eye was lost to follow-up after initial treatment and was excluded. The mean (±SD, median) duration of follow-up was 17.1 (±12.8, 11.7) months and 20.3 (±11.4, 15.1) months for SGDD and CPC, respectively ( P =0.42, 2 sample t test). The mean total direct costs (±SD, median) per patient during the study period were $8790 (±$3421, $6805 for the SGDD group) and $4090 (±$1424, $3566) for the CPC group ( P <0.001). Similarly, the global period cost was higher in the SGDD group than in the CPC group [$6173 (±$830, $5861) vs. $2569 (±$652, $2628); P <0.001]. The monthly cost after the 90-day global period was $215 (±$314, $100) for SGDD and $103 (±$74, $86) for CPC ( P =0.31). The cost of IOP-lowering medications was not significantly different between groups during the global period ( P =0.19) or after the global period ( P =0.23). CONCLUSION: The total direct cost in the SGDD group was more than double that in the CPC group, driven largely by the cost of the study procedure. The costs of IOP-lowering medications were not significantly different between groups. When considering treatment options for patients with a failed primary GDD, clinicians should be aware of differences in costs between these treatment strategies.

Comparison of Outcomes From Delayed-Onset Bleb-Related Endophthalmitis Treated With Pars Plana Vitrectomy Versus Vitreous Biopsy.

PRCIS: Bleb-related endophthalmitis (BRE) is a serious complication of glaucoma filtration surgery. The current study reports similar visual and intraocular pressure (IOP) outcomes in eyes treated with pars plana vitrectomy (PPV) compared with vitreous biopsy and injection of intravitreal antibiotics (TI). PURPOSE: The purpose of this study was to investigate the isolated organisms, visual acuity (VA), and IOP outcomes associated with delayed-onset BRE in eyes treated with PPV versus TI. PATIENTS AND METHODS: A retrospective chart review was conducted at the Bascom Palmer Eye Institute (Miami, Florida) and the University of Florida (Gainesville, FL) identifying patients treated for BRE with at least 1 month of follow-up from the inception of an electronic health record (2014 and 2011, respectively) through 2021. All patients had undergone bleb-forming glaucoma surgery at least 1 month before endophthalmitis diagnosis. RESULTS: Thirty-nine eyes from 39 patients (33 from Bascom Palmer, 6 from University of Florida) were included. Trabeculectomy was performed in 34 of 39 eyes (87.2%). Streptococcus species (9 eyes, 23.1%) and Staphylococcus species (8 eyes, 20.5%) were the most common isolated organisms and were similar in both treatment groups ( P =0.49). Baseline VA was worse in the PPV group (logarithm of the minimum angle of resolution: 2.51 vs. 2.16, P =0.04), but VA at last follow-up was similar ( P =0.48) in both groups. After recovery from BRE, the average IOP in the PPV group was 15.1 mm Hg on 0.9 IOP-lowering medications compared with 12.6 mm Hg on 1.2 medications in the TI group (IOP: P =0.56; medications: P =0.80). Additional glaucoma surgery was performed in 44.4% of the PPV eyes and 16.7% of the TI eyes ( P =0.09). CONCLUSION: In eyes with delayed-onset BRE, isolated organisms, visual outcomes, and IOP control were similar after initial PPV compared with TI.

Outcomes of the Second Aqueous Shunt Implant Versus Transscleral Cyclophotocoagulation Treatment Study: A Randomized Comparative Trial.

PRCIS: Short-term overall success rates were high with either SGDD or CPC. However, SGDD was associated with more clinic visits and an increased risk of additional glaucoma surgery. Both treatments were reasonable options for eyes with inadequately controlled IOP after a single GDD. PURPOSE: The purpose of this study is to compare the implantation of a second glaucoma drainage device (SGDD) and transscleral cyclophotocoagulation (CPC) in eyes with inadequately controlled intraocular pressure (IOP), despite the presence of a preexisting glaucoma drainage device. METHODS: Patients with inadequately controlled IOP, despite the medical therapy and a preexisting glaucoma drainage device, were enrolled at 14 clinical centers and randomly assigned to treatment with a SGDD or CPC. MAIN OUTCOME MEASURES: Surgical failure was defined as: (1) IOP ≤5 mm Hg or >18 mm Hg or <20% reduction below baseline on maximum tolerated topical ocular hypotensive therapy, (2) reoperation for glaucoma, or (3) loss of light perception. The primary outcome measure was overall success with or without adjunctive medical therapy. RESULTS: Forty-two eyes of 42 participants were randomized to SGDD (n=22) or CPC (n=20). Mean duration of follow-up was 18.6 (±12.1; range: 1.1-38.6) months. The cumulative success rate was 79% for SGDD and 88% for CPC at 1 year ( P =0.63). Although the study was underpowered, no significant differences in IOP, postoperative number of IOP-lowering medications, or adverse events were observed. The number of additional glaucoma surgeries ( P =0.003), office visits during the first 3 months ( P <0.001), and office visits per month after month 3 ( P <0.001) were greater in the SGDD group. CONCLUSIONS: Short-term overall success rates were high with either SGDD or CPC. However, SGDD was associated with more clinic visits and an increased risk of additional glaucoma surgery.

Reversal of retinal ganglion cell dysfunction after surgical reduction of intraocular pressure.

PURPOSE: The pattern electroretinogram optimized for glaucoma screening (PERGLA) is a noninvasive method of objectively measuring retinal ganglion cell (RGC) function. This study was undertaken to quantify the RGC response to intraocular pressure (IOP) reduction after glaucoma surgery. DESIGN: Prospective cohort study. PARTICIPANTS: Forty-seven eyes of 47 patients with uncontrolled IOP or progressive glaucomatous optic neuropathy receiving maximal medical therapy requiring trabeculectomy or aqueous drainage device implantation who met eligibility criteria. METHODS: Eyes with visual acuity less than 20/30, corneal or retinal pathologic features, or unreliable standard automated perimetry (SAP) results were excluded. All patients underwent complete ocular examination, arterial blood pressure, SAP, and PERGLA at 2 sessions before surgery and at 3 months after surgery. Mean ocular perfusion pressure (MOPP) was calculated. Each measure of PERGLA amplitude and phase was an average of 600 artifact-free signal registrations. MAIN OUTCOME MEASURES: Intraocular pressure and PERGLA amplitude and phase. RESULTS: Forty-seven eyes of 47 patients (mean age ± standard deviation [SD], 69.9 ± 11.3 years) were enrolled. Thirty-four eyes (72%) underwent trabeculectomy with antifibrosis therapy; 13 eyes (28%) underwent glaucoma drainage implant surgery. Mean ± SD postoperative IOP (10.4 ± 4.6 mmHg) was significantly (P< 0.001) reduced compared with that before surgery (19.7 ± 8.6 mmHg). Mean ± SD postoperative PERGLA amplitude (0.46 ± 0.22 µV) was significantly (P = 0.001) increased compared with preoperative PERGLA amplitude (0.37 ± 0.18 µV). Mean ± SD postoperative PERGLA phase (1.72 ± 0.20 π-radian) was significantly (P = 0.01) reduced compared with preoperative PERGLA phase (1.81 ± 0.22 π-radian). Mean ± SD postoperative MOPP (53.1 ± 6.4 mmHg) was significantly (P < 0.001) increased compared with mean ± SD preoperative MOPP (45.8 ± 10.1 mmHg). No correlation (P > 0.05) was identified between change in PERGLA amplitude and change in IOP or MOPP. CONCLUSIONS: Reversal of RGC dysfunction occurs after surgical reduction of IOP and may be quantified using PERGLA.

Secondary open-angle glaucoma and serous macular detachment associated with pulmonary hypertension.

PURPOSE: We describe a patient with secondary open-angle glaucoma and serous macular detachment associated with pulmonary hypertension. OBSERVATIONS: A 59 year-old male with pulmonary hypertension presented with vision loss and was noted to have bilateral engorged epibulbar vessels, blood in Schlemm's canal, elevated intraocular pressure, retinal venous tortuosity and serous retinal detachments. Enhanced depth optical coherence tomography (ED-OCT) showed bilateral serous macular detachments with marked choroidal thickening. Fluorescein angiography and indocyanine green angiography revealed choroidal vascular congestion and engorgement. Improvement of subretinal fluid was achieved with systemic control of his venous hypertension, and the intraocular pressure responded to medical anti-glaucoma therapy. CONCLUSIONS: Pulmonary hypertension may be associated with secondary open-angle glaucoma, choroidal engorgement and serous macular detachment, and should be considered in the differential diagnosis of elevated episcleral venous pressure. Management of ocular complications is challenging and requires a multi-disciplinary approach.

Efficacy and safety of ultrasonic circular cyclocoagulation with second-generation probe in glaucoma: A retrospective study.

BACKGROUND: To assess the efficacy and safety of the second-generation probe of ultrasonic circular cyclocoagulation (UC3) in naive or refractory glaucoma, with a 6-month follow-up. METHODS: A retrospective consecutive case-series study included patients having a UC3 procedure with the second-generation probe of the EyeOP1 device, intraocular pressure (IOP) ≥ 21 mmHg and under maximum tolerated medical treatment, with or without previous glaucoma surgery. Surgical success was defined at the 6-month post-operative visit as IOP > 5 and ≤ 21 mmHg with IOP reduction ≥ 20% from baseline, without any reoperation, and visual acuity better than negative light perception. RESULTS: 100 patients were included and 97 (97.0%; 97 eyes) attended the 6-month follow-up. At 6 months, surgical success was obtained in 48 eyes (49.5%). Intraocular pressure was reduced from a mean ± SD preoperative value of 28.0 ± 5.6 mmHg to 19.3 ± 7.1 mmHg at 6 months (p<0.0001). The proportion of eyes requiring oral acetazolamide decreased from 57.0% to 30.0% between baseline and 6 months after surgery (p = 0.0007). We observed 15 (15.0%) cases of postsurgical macular edema, 8 (8.0%) of hypotony, and 20 (20.0%) of visual acuity loss > 2 Snellen lines. Postsurgical macular edema was associated with a history of epiretinal membranes, uveitis or retinal detachment. Risk factors for hypotony were a history of diabetes or trabeculectomy. CONCLUSIONS: The second-generation UC3 probe significantly reduced IOP in eyes with naive and refractory glaucoma but severe post-operative complications were often observed. Further studies are needed to better identify responders and decrease the high risk for complications associated with the procedure.

Malignant Glaucoma After Laser Peripheral Iridotomy.

PURPOSE: We describe a patient with primary angle-closure glaucoma who developed malignant glaucoma following laser peripheral iridotomy. METHODS: A 58-year-old male presented with peripheral and central anterior chamber shallowing following an uncomplicated Nd: YAG laser peripheral iridotomy. Intraocular pressure (IOP) and B-scan echography were normal, and there was -1.5 Ddiopter asymmetric myopia. Despite treatment with aqueous suppression and cycloplegia for 7 months, the patient developed progressive myopic shift and anterior chamber shallowing. RESULTS: The patient underwent 23-G pars plana vitrectomy and lensectomy using a standard 3-port technique, and sulcus posterior chamber intraocular lens implantation in the left eye. Twelve months postoperatively, the anterior chamber has remained deep, best-corrected visual acuity is 20/15, and the IOP is 11 mm Hg. CONCLUSIONS: Malignant glaucoma is a rare complication of laser iridotomy and should be considered in eyes with progressive anterior chamber shallowing and myopia despite normal IOP.

A Comparison of Resource Use and Costs of Caring for Patients With Exfoliation Syndrome Glaucoma Versus Primary Open-Angle Glaucoma.

PURPOSE: To characterize differences in resource utilization and cost of managing enrollees with exfoliation glaucoma (XFG) compared to primary open-angle glaucoma (POAG). DESIGN: Retrospective utilization and cost comparison using Medicare claims data. METHODS: We identified Medicare beneficiaries with XFG or POAG and ≥5 years of continuous enrollment from January 2008 to December 2014. We distinguished newly diagnosed cases from those with preexisting disease. We compared ophthalmic resource utilization and costs over 2 years of follow-up for persons with newly diagnosed and preexisting XFG vs those with POAG. Main outcome measures were number of clinic visits, diagnostic procedures, medication fills, laser and incisional surgery, and mean eye care costs per beneficiary. RESULTS: Among 192 eligible enrollees (median age 77.6 years) with newly diagnosed XFG and 7339 enrollees (median age 77.3 years) with newly diagnosed POAG, those with XFG had more office visits (mean, 9.1 vs 7.9; P = .001), cataract surgery (34.9% vs 19.0%; P < .0001), and glaucoma surgery (28.7% vs 19.7%, P = .002). They also experienced 27% higher mean total eye care costs ($3260 vs $2562, P = .0001) over 2 years of follow-up. Among 2745 enrollees (median age 80.5 years) with preexisting XFG and 89 036 persons (median age 79.5) with preexisting POAG, persons with XFG had more office visits (mean 9.3 vs 7.3; P < .0001), perimetry (85.3% vs 79.8%; P < .0001), cataract surgery (23.4% vs 12.3%; P < .0001), laser trabeculoplasty (18.6% vs 9.6%; P < .0001), and trabeculectomy (8.1 vs 1.8%; P < .0001) and experienced 37% higher total mean eye care costs ($3764 vs $2739; P < .0001). CONCLUSIONS: Healthcare resource utilization and costs are substantially higher for managing patients with XFG compared to POAG.

Detecting Glaucoma Progression Using Guided Progression Analysis with OCT and Visual Field Assessment in Eyes Classified by International Classification of Disease Severity Codes.

PURPOSE: To compare the detection and rates of progressive retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) loss with spectral-domain (SD) OCT and visual field (VF) loss using Guided Progression Analysis (GPA; Carl Zeiss Meditec, Dublin, CA) in glaucomatous eyes classified using International Classification of Diseases (ICD) diagnosis codes. DESIGN: Retrospective cohort study. PARTICIPANTS: Glaucoma patients with at least 3 years of follow-up and a minimum of 4 SD OCT and 5 reliable VF examinations. METHODS: Glaucoma severity was classified using ICD, 10th Edition, Clinical Modification, diagnosis codes. Rates of RNFL, macular GCIPL, and VF loss were calculated, and progression estimates were compared using generalized estimating equations and McNemar's tests. MAIN OUTCOME MEASURES: Progressive RNFL, GCIPL, and VF loss assessed by GPA criteria. RESULTS: A total of 147 eyes of 116 patients (mean age, 69.9±8.5 years) were included with mean follow-up of 69.67±18.64 months. Overall, 38 of 147 eyes (25.9%) showed RNFL progression, 35 eyes (23.8%) showed GCIPL progression, and 20 eyes (13.6%) showed VF progression. Progression by all 3 methods was noted in 10 eyes (7.0%). Eyes with mild (n = 62) and severe (n = 46) glaucoma showed significantly more progression on SD OCT compared with VF (P < 0.001 and P = 0.004). Retinal nerve fiber layer, GCIPL, and VF progressors showed faster rates of loss in average RNFL, GCIPL, and VF mean deviation compared with nonprogressors (mean ± standard error: -1.47±0.30 µm/year vs. -0.03±0.12 µm/year [P = 0.0001], -1.68±0.34 µm/year vs. -0.29±0.07 µm/year [P = 0.0001], and -1.07±0.20 dB/year vs. -0.19±0.04 dB/year [P = 0.0001], respectively). CONCLUSIONS: Spectral-domain OCT progression was significantly more common than VF progression in glaucomatous eyes classified with mild and severe disease. Structure and function should be monitored closely across the entire spectrum of glaucoma severity.

Estimating Visual Field Mean Deviation using Optical Coherence Tomographic Nerve Fiber Layer Measurements in Glaucoma Patients.

To construct an optical coherence tomography (OCT) nerve fiber layer (NFL) parameter that has maximal correlation and agreement with visual field (VF) mean deviation (MD). The NFL_MD parameter in dB scale was calculated from the peripapillary NFL thickness profile nonlinear transformation and VF area-weighted averaging. From the Advanced Imaging for Glaucoma study, 245 normal, 420 pre-perimetric glaucoma (PPG), and 289 perimetric glaucoma (PG) eyes were selected. NFL_MD had significantly higher correlation (Pearson R: 0.68 vs 0.55, p < 0.001) with VF_MD than the overall NFL thickness. NFL_MD also had significantly higher sensitivity in detecting PPG (0.14 vs 0.08) and PG (0.60 vs 0.43) at the 99% specificity level. NFL_MD had better reproducibility than VF_MD (0.35 vs 0.69 dB, p < 0.001). The differences between NFL_MD and VF_MD were -0.34 ± 1.71 dB, -0.01 ± 2.08 dB and 3.54 ± 3.18 dB and 7.17 ± 2.68 dB for PPG, early PG, moderate PG, and severe PG subgroups, respectively. In summary, OCT-based NFL_MD has better correlation with VF_MD and greater diagnostic sensitivity than the average NFL thickness. It has better reproducibility than VF_MD, which may be advantageous in detecting progression. It agrees well with VF_MD in early glaucoma but underestimates damage in moderate~advanced stages.

Predictive Factors for the Rate of Visual Field Progression in the Advanced Imaging for Glaucoma Study.

PURPOSE: To investigate predictive factors associated with the rate of visual field (VF) loss in open-angle glaucoma. DESIGN: Prospective multicenter cohort study. METHODS: Perimetric glaucoma patients of the Advanced Imaging for Glaucoma study were selected for analysis if they had 9 completed visits. Confirmed rapid significant progression (CRSP) of VF was defined as a significant (P < 0.05) negative VF index (VFI) slope of -1%/year or a mean deviation slope of -0.5 dB/year, confirmed at 2 consecutive follow-up visits. Slow progression was defined as VFI slope greater than -0.5%/year or a mean deviation slope of -0.25 dB/year. Fourier-domain optical coherence tomography (FD-OCT) measured optic disc, peripapillary retinal nerve fiber layer (NFL), and macular ganglion cell complex (GCC) thicknesses. Logistic regression was used to identify baseline predictors for CRSP and slow progression. Linear regression was used to identify baseline predictors for the VFI and mean deviation slope. RESULTS: Eyes (n = 150) of 103 participants were included. Slow progression was observed in 80 eyes (53.3%) and CRSP in 23 eyes (15.3%). Larger NFL and GCC baseline focal loss volume (FLV), thinner central corneal thickness, and lower VFI were significant (P < 0.05) baseline predictors of more rapid progression on univariate analysis. The predictor with the highest odds ratio (OR) was NFL-FLV, which was also the most significant non-VF predictor in the multivariate analysis. Eyes with NFL-FLV >8.5% had an OR of 2.67 for CRSP and 0.42 for slow progression. Disc hemorrhage during the follow-up was also important, with an OR of 2.61 for CRSP and 0.23 for slow progression for each occurrence. CONCLUSIONS: Focal loss measured by FD-OCT or VF along with CCT are strong baseline predictors for the rate of glaucoma progression.

Combining nerve fiber layer parameters to optimize glaucoma diagnosis with optical coherence tomography.

PURPOSE: To identify the best combination of Stratus optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness parameters for the detection of glaucoma. DESIGN: Observational cross-sectional study. PARTICIPANTS: Eighty-nine age-matched normal and perimetric glaucoma participants enrolled in the Advanced Imaging for Glaucoma Study. METHODS: The Zeiss Stratus OCT system was used to obtain the circumpapillary RNFL thickness in both eyes of each participant. Right and left eye clock-hour data are analyzed together, assuming mirror-image symmetry. The RNFL diagnostic parameters were combined using either or-logic or and-logic approaches. MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AROC), sensitivity, and specificity are used to evaluate diagnostic performance. RESULTS: Overall average RNFL thickness has the highest AROC value (0.89) of all single parameters evaluated, followed by the inferior and superior quadrants (0.88 and 0.86, respectively). The clock hours with the best AROC values are in the inferior and superior quadrants. The highest AROC (0.92) was achieved by the or-logic combination of overall, inferior, and superior quadrant RNFL thicknesses. The 3-parameter combination was significantly better than the overall average alone (P = 0.01). The addition of more quadrants or clock hours to the combination reduced diagnostic performance. CONCLUSIONS: The best stand-alone diagnostic strategy for Stratus OCT RNFL data is to classify an eye as glaucomatous if the overall, inferior quadrant, or superior quadrant RNFL thickness average is below normal.

Role of optic nerve imaging in glaucoma clinical practice and clinical trials.

PURPOSE: To provide an update on the role of optic nerve and peripapillary retinal nerve fiber layer imaging in glaucoma clinical practice and clinical trials. DESIGN: Perspective. METHODS: Review of recent literature and authors' clinical and laboratory studies. RESULTS: Imaging technologies such as confocal scanning laser ophthalmoscopy, scanning laser polarimetry, and optical coherence tomography provide objective and quantitative measurements that are highly reproducible and show very good agreement with clinical estimates of optic nerve head structure and visual function. Structural assessments provided by imaging complement optic disk photography in clinical care and have the potential to identify relevant structural efficacy endpoints in glaucoma randomized clinical trials. As with other technologies, imaging may produce false identification of glaucoma and its progression; thus, clinicians should not make management decisions based solely on the results of one single test or technology. CONCLUSIONS: Although optic disk stereophotography represents the standard for documentation of glaucomatous structural damage in practice and research trials, advances in computerized imaging technology provide useful measures that assist the clinician in glaucoma diagnosis and monitoring and offer considerable opportunity for use as efficacy endpoints in clinical trials.