Improving IVF Utilization with Patient-Centric Artificial Intelligence-Machine Learning (AI/ML): A Retrospective Multicenter Experience.

Objectives: In vitro fertilization (IVF) has the potential to give babies to millions more people globally, yet it continues to be underutilized. We established a globally applicable and locally adaptable IVF prognostics report and framework to support patient-provider counseling and enable validated, data-driven treatment decisions. This study investigates the IVF utilization rates associated with the usage of machine learning, center-specific (MLCS) prognostic reports (the Univfy® report) in provider-patient pre-treatment and IVF counseling. Methods: We used a retrospective cohort comprising 24,238 patients with new patient visits (NPV) from 2016 to 2022 across seven fertility centers in 17 locations in seven US states and Ontario, Canada. We tested the association of Univfy report usage and first intra-uterine insemination (IUI) and/or first IVF usage (a.k.a. conversion) within 180 days, 360 days, and "Ever" of NPV as primary outcomes. Results: Univfy report usage was associated with higher direct IVF conversion (without prior IUI), with odds ratios (OR) 3.13 (95% CI 2.83, 3.46), 2.89 (95% CI 2.63, 3.17), and 2.04 (95% CI 1.90, 2.20) and total IVF conversion (with or without prior IUI), OR 3.41 (95% CI 3.09, 3.75), 3.81 (95% CI 3.49, 4.16), and 2.78 (95% CI 2.59, 2.98) in 180-day, 360-day, and Ever analyses, respectively; p < 0.05. Among patients with Univfy report usage, after accounting for center as a factor, older age was a small yet independent predictor of IVF conversion. Conclusions: Usage of a patient-centric, MLCS-based prognostics report was associated with increased IVF conversion among new fertility patients. Further research to study factors influencing treatment decision making and real-world optimization of patient-centric workflows utilizing the MLCS reports is warranted.

Long-term outcomes of treat-and-extend ranibizumab with and without navigated laser for diabetic macular oedema: TREX-DME 3-year results.

BACKGROUND/AIMS: To evaluate the long-term effects of treat-and-extend dosing of ranibizumab with and without navigated focal laser for diabetic macular oedema (DME). METHODS: This is a multicentre, randomised clinical trial where 150 eyes were randomised into three cohorts; Monthly (n=30), TReat and EXtend without macular laser photocoagulation (TREX; n=60), and treat and extend with angiography-GuIded macular LAser photocoagulation (GILA; n=60). During the first 2 years, eyes either received ranibizumab 0.3 mg every 4 weeks or underwent treat-and-extend ranibizumab with or without angiography-guided laser therapy. In the third year, all eyes were treated as needed with ranibizumab for >5 letters vision loss or if the central retinal thickness (CRT) was >325 µm, and all eyes were eligible to receive focal laser. RESULTS: 109 eyes (73%) completed the 3-year end-point. At week 156, mean best-corrected visual acuity (BCVA) and CRT improved by 6.9, 9.7, 9.5 letters (p=0.60) and 129, 138, 165 µm (p=0.39), in the Monthly, TREX and GILA cohorts, respectively. These improvements were reached prior to week 104 and no significant changes occurred from week 104 to week 156 (BCVA: p=0.34; CRT: p=0.36). The mean number of injections in the third year was 3.0, 3.1, and 2.4 in the Monthly, TREX and GILA cohorts, respectively (p=0.56). 86 eyes (79%) required at least one ranibizumab injection in the third year. CONCLUSION: The improvements achieved after 2 years of treat-and-extend ranibizumab for DME were maintained in the third year with a mean of 3 intravitreal injections. TRIAL REGISTRATION NUMBER: FDA IND 119146, NCT01934556.

Randomized Trial of Treat and Extend Ranibizumab With and Without Navigated Laser Versus Monthly Dosing for Diabetic Macular Edema: TREX-DME 2-Year Outcomes.

PURPOSE: To prospectively evaluate a treat and extend algorithm of ranibizumab with and without navigated laser to monthly dosing for center-involving diabetic macular edema. DESIGN: This was a multicenter, randomized, clinical trial. METHODS: One hundred fifty eyes were randomized into 3 cohorts: monthly (n = 30), treat and extend without laser photocoagulation (TREX; n = 60), and treat and extend with angiography-guided laser photocoagulation (GILA; n = 60). Monthly cohort eyes received ranibizumab 0.3 mg every 4 weeks. TREX and GILA cohort eyes received 4 monthly injections of ranibizumab 0.3 mg followed by a treat and extend dosing strategy. GILA cohort eyes also received navigated focal laser at month 1 and again every 3 months as needed. The primary outcomes included the mean change in best-corrected visual acuity and central retinal thickness and the number of injections from baseline to 2 years. RESULTS: At 2 years, mean best-corrected visual acuity and central retinal thickness improved by 7.5, 9.6, and 9.0 letters (P = .75) and 139, 140, and 175 µm (P = .09), in the monthly, TREX, and GILA cohorts, respectively. The mean number of injections was significantly reduced in both the TREX (18.9) and GILA (17.5) cohorts compared with the monthly cohort (24.7, P < .001). Between the TREX and GILA cohorts, there was no significant difference in the mean treatment interval, mean maximal treatment interval, or percentage of eyes extended to 12 weeks. The total 2-year incidence of Anti-Platelet Trialists' Collaboration events was 6.7%. CONCLUSION: The treat and extend algorithm of ranibizumab in the TREX-DME trial resulted in significantly fewer injections and yielded visual and anatomic gains comparable to monthly dosing at 2 years.

Paradoxical Anatomic Response to Topical Carbonic Anhydrase Inhibitor in X-linked Retinoschisis.

An 11-year-old boy presented for central vision blurring in each eye. Visual acuity was 20/80 and examination revealed spoke-wheel foveal schisis and peripheral elevated diaphanous inner retina in each eye. Spectral-domain optical coherence tomography showed inner-retinal, flat-topped cysts in each eye. Electrophysiologic testing was refused, but a clinical diagnosis of X-linked retinoschisis was made. Three months after topical dorzolamide (Trusopt; Santen Pharmaceutical, Osaka, Japan) was started, the macular cysts worsened significantly. The medication was stopped and 3 months later, the macular anatomy returned to baseline. Physicians should be aware of this potential paradoxical anatomic response to topical carbonic anhydrase inhibitor therapy in X-linked retinoschisis. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:142-144.].

Neovascular age-related macular degeneration management in the third year: final results from the TREX-AMD randomised trial.

BACKGROUND/AIMS: Prospectively evaluate outcomes in the third year of neovascular age-related macular degeneration (AMD) management using ranibizumab with continued treat and extend (TREX) dosing compared with monthly visits with retreatment upon evidence of exudative disease activity (PRN, pro re nata). METHODS: Subjects with treatment-naïve neovascular AMD were randomised 1:2 to Monthly or TREX and managed through 2 years. In the third year, subjects randomised to Monthly were managed PRN while subjects randomised to TREX were continued on TREX dosing or transitioned to PRN after achieving an interval of 12 weeks between visits. RESULTS: Sixty subjects enrolled and 46 (77%) completed month 36 (M36). Transition from Monthly to PRN was associated with a decline in best corrected visual acuity (BCVA) (+10.5 letters (month 24) to +5.4 (M36, p=0.09)); three (15%) subjects required no dosing during year 3, and 47% (114/243) of possible PRN injections were delivered, yielding a mean of 6.1 injections during year 3. Among the 9 (23%) TREX subjects transitioned to PRN, the need for ongoing anti-vascular endothelial growth factor retreatments was small, with 4 (4%) intravitreal injections being delivered among 106 PRN visits; this subgroup displayed an inferior BCVA trajectory compared with the remainder of subjects. Outcomes among subjects continued on TREX were more favourable, with a mean gain of +5.0 letters at M36. CONCLUSIONS: Upon transition to PRN, subjects randomised to monthly dosing experienced a decline in BCVA. Among subjects initially randomised to TREX who transitioned to PRN after achieving a 12-week interval between visits, the overall need for additional treatment was low. TRIAL REGISTRATION NUMBER: NCT01748292, Results.

Relationship Between Visual Acuity and Retinal Thickness During Anti-Vascular Endothelial Growth Factor Therapy for Retinal Diseases.

PURPOSE: To investigate the relationship between best-corrected visual acuity (BCVA) and central retinal thickness (CRT) in eyes receiving ranibizumab for 3 common retinal diseases. DESIGN: Retrospective analysis of clinical trial data. METHODS: Early Treatment Diabetic Retinopathy Study BCVA and spectral-domain optical coherence tomography-measured CRT of 387 eyes of 345 patients enrolled in 6 prospective clinical trials for management of neovascular age-related macular degeneration (AMD), diabetic macular edema (DME), and retinal vein occlusion (RVO) were evaluated by Pearson correlation and linear regression. RESULTS: At baseline, there was a small correlation between BCVA and CRT in pooled AMD trial data (r = -0.24). A medium correlation was identified in pooled DME trial data (r = -0.42). No correlation was found in pooled RVO trial data. At month 12, no correlation was found between changes from baseline in BCVA and CRT in pooled AMD trial data. Medium correlations were identified in both pooled DME (r = -0.45) and pooled RVO (r = -0.35) trial data at month 12. Changes in BCVA and CRT associated with edema recurrence upon transition from monthly to pro re nata (PRN) dosing were correlated in AMD (r = -0.27) and RVO (r = -0.72) trials, but not in DME trial data. CONCLUSION: DME demonstrated a convincing relationship between BCVA and CRT. Correlations appear to be more complex in AMD and RVO. At the inflection point between monthly and PRN dosing, when recurrence of edema is anticipated in many patients, CRT appears strongly correlated with loss of BCVA in RVO.

Teleophthalmology image-based navigated retinal laser therapy for diabetic macular edema: a concept of retinal telephotocoagulation.

BACKGROUND: To determine the feasibility and efficacy of a retinal telephotocoagulation treatment plan for diabetic macular edema. METHODS: Prospective, interventional cohort study at two clinical sites. Sixteen eyes of ten subjects with diabetic macular edema underwent navigated focal laser photocoagulation using a novel teleretinal treatment plan. Clinic 1 (King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia) collected retinal images and fundus fluorescein angiogram. Clinic 2 (Palmetto Retina Center, West Columbia, SC, USA) created image-based treatment plans based on which macular laser photocoagulation was performed back at clinic 1. The primary outcome of the study was feasibility of image transfer and performing navigated laser photocoagulation for subjects with diabetic macular edema between two distant clinics. Secondary measures were change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) by spectral-domain optical coherence tomography at 3 months after treatment. RESULTS: The teleretinal treatment plan was able to be successfully completed in all 16 eyes. The mean logMAR BCVA at baseline was 0.49 ± 0.1, which remained stable (0.45 ± 0.1) 3 months after treatment (p = 0.060). The CRT improved from 290.1 ± 37.6 µm at baseline to 270.8 ± 27.7 µm 3 months after treatment (p = 0.005). All eyes demonstrated improvement in the area of retinal edema after laser photocoagulation, and no eyes demonstrated visual acuity loss 3 months after treatment. CONCLUSION: This study introduces the concept of retinal telephotocoagulation for diabetic macular edema, and demonstrates the feasibility and safety of using telemedicine to perform navigated retinal laser treatments regardless of geographical distance.

Randomized Trial of Treat-and-Extend versus Monthly Dosing for Neovascular Age-Related Macular Degeneration: 2-Year Results of the TREX-AMD Study.

PURPOSE: To evaluate a prospective treat-and-extend (TREX) management strategy compared with monthly dosing with intravitreal ranibizumab (Lucentis) in neovascular age-related macular degeneration (AMD). DESIGN: Prospective, randomized, multicenter clinical trial. PARTICIPANTS: Sixty patients with treatment-naïve neovascular AMD randomized 1:2 to monthly or TREX cohorts. METHODS: Patients with Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) of 20/32 to 20/500 (Snellen equivalent) were randomized to receive intravitreal 0.5 mg ranibizumab monthly or, according to a TREX protocol, no less frequently than every 12 weeks. After interval extension, if recurrent exudative disease was identified, this maximum interval between treatments was rechallenged according to a strict prospective protocol. MAIN OUTCOME MEASURE: Change in ETDRS BCVA from baseline. RESULTS: Sixty patients were enrolled and 50 completed month 24, at which point mean ETDRS BCVA letter gains were similar: 10.5 and 8.7 for the monthly and TREX cohorts, respectively (P = 0.64). At month 24, 4 patients (20%) and 12 patients (30%) in the monthly and TREX cohorts, respectively, gained at least 15 letters (P = 0.41). No monthly cohort patient lost more than 2 letters, whereas 5 TREX cohort patients (13%) lost at least 15 letters. Anatomic improvements were similar between the cohorts. Through month 24, the mean number of injections administered was 25.5 (range, 22-27) and 18.6 (range, 10-25) for the monthly and TREX cohorts, respectively (P < 0.001). Among TREX patients completing month 24, 14 (47%) were at an extension interval of 8 weeks or more, and the mean maximum tolerated extension was 8.5 weeks over the course of 2 years. Of the 26 TREX patients (65%) who demonstrated recurrent exudation upon interval extension, the first maximum extension interval was consistent in most eyes (n = 19 [73%]). CONCLUSIONS: The TREX neovascular AMD management protocol used with ranibizumab in the Treat-and-Extend Protocol in Patients with Wet Age-Related Macular Degeneration (TREX-AMD) study resulted in visual and anatomic gains comparable with those obtained with monthly dosing, and most patients randomized to TREX therapy demonstrated a relatively consistent maximum extension interval.

Randomized Trial of Treat and Extend Ranibizumab with and without Navigated Laser for Diabetic Macular Edema: TREX-DME 1 Year Outcomes.

PURPOSE: To compare monthly dosing with a treat and extend algorithm using ranibizumab 0.3 mg with and without angiography-guided macular laser photocoagulation for center-involving diabetic macular edema (DME). DESIGN: Multicenter, prospective, randomized clinical trial. PARTICIPANTS: A total of 150 eyes from 116 subjects were randomized into 3 cohorts: Monthly (n = 30), TReat and EXtend without macular laser photocoagulation (TREX; n = 60), and treat and extend with angiography-GuIded macular LAser photocoagulation (GILA; n = 60). METHODS: Monthly cohort eyes received ranibizumab 0.3 mg every 4 weeks. Eyes in the TREX and GILA cohorts received 4 monthly injections of ranibizumab 0.3 mg followed by a treat and extend algorithm based on disease activity. Eyes in the GILA cohort also received angiography-guided macular laser photocoagulation at month 1 and again every 3 months for microaneurysm leakage. MAIN OUTCOME MEASURES: Change in mean best-corrected visual acuity (BCVA), mean central retinal thickness (CRT), number of injections from baseline to 1 year, and percentage gaining/losing 2 and 3 lines of vision. RESULTS: Baseline demographics were well balanced among the cohorts. A total of 137 eyes (91%) completed the 1-year end point visit. At 1 year, the mean BCVA improved by 8.6, 9.6, and 9.5 letters in the Monthly, TREX, and GILA cohorts, respectively (P = 0.8). There was no significant difference between the cohorts in the percentage gaining/losing 2 and 3 lines of vision. The CRT improved by 123 µm, 146 µm, and 166 µm in the Monthly, TREX, and GILA cohorts, respectively (P = 0.47). The mean number of macular laser treatments in the GILA cohort at 1 year was 2.9 (range, 1-4). The number of injections was significantly reduced in both the TREX (10.7) and GILA (10.1) cohorts compared with the Monthly cohort (13.1, P < 0.001). There were no cases of endophthalmitis, and the total incidence of Anti-Platelet Trialists' Collaboration events was 4.7%. CONCLUSIONS: This prospective, randomized trial found that treat and extend dosing of ranibizumab 0.3 mg with and without angiography-guided macular laser photocoagulation significantly decreased the number of injections given while providing similar visual and anatomic outcomes compared with monthly dosing at 1 year. Adding angiography-guided laser photocoagulation to this dosing algorithm did not significantly improve outcomes at 1 year.

SEVERE PANUVEITIS, RETINAL VASCULITIS, AND OPTIC DISK GRANULOMA SECONDARY TO SARCOIDOSIS.

PURPOSE: To report a case of panuveitis, retinal vasculitis, and optic disk granuloma due to sarcoidosis. METHODS: Case report and literature review. RESULTS: A 26-year-old previously healthy African American male presented with four months of gradual progressive visual decline in the right eye. Clinical examination revealed severe panuveitis, retinal vasculitis, and large optic nerve mass lesion. Diffuse supraclavicular lymphadenopathy was also present. Histopathologic examination of the lymph node biopsy revealed granulomatous inflammation with some areas of caseous necrosis consistent with sarcoidosis. CONCLUSION: Sarcoidosis is a common cause of uveitis and retinal vasculitis. In rare cases, an optic disk granuloma may occur and can be treated with immunosuppressive therapy.

Prospective Trial of Treat-and-Extend versus Monthly Dosing for Neovascular Age-Related Macular Degeneration: TREX-AMD 1-Year Results.

PURPOSE: To assess prospectively a treat-and-extend (TREX) management strategy compared with monthly dosing of intravitreal ranibizumab in treatment-naïve neovascular age-related macular degeneration (AMD) patients. DESIGN: Phase IIIb, multicenter, randomized, controlled clinical trial. PARTICIPANTS: Sixty patients with treatment-naïve neovascular AMD randomized 1:2 to monthly or TREX management. METHODS: Patients with Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) from 20/32 to 20/500 (Snellen equivalent) were randomized to receive intravitreal 0.5 mg ranibizumab monthly or according to a TREX protocol. The TREX patients were treated monthly for at least 3 doses, until resolution of clinical and spectral-domain optical coherence tomography evidence of exudative disease activity; the interval between visits then was individualized according to a strict prospective protocol. MAIN OUTCOME MEASURES: Mean ETDRS BCVA change from baseline. RESULTS: At baseline, mean age was 77 years (range, 59-96 years), mean BCVA was 20/60 (Snellen equivalent), and mean central retinal thickness (CRT) was 511 µm. Fifty-seven eyes (95%) completed month 12, at which point mean BCVA improved by 9.2 and 10.5 letters in the monthly and TREX cohorts, respectively (P = 0.60). The mean number of injections administered through month 12 was 13.0 and 10.1 (range, 7-13) in the monthly and TREX cohorts, respectively (P < 0.0001). Among TREX patients, 7 (18%) were maximally extended, 4 (10%) demonstrated fluid at every visit, and at month 12, 18 (45%) had achieved an extension interval of 8 weeks or more; the mean maximum extension interval between injections after the first 3 monthly doses was 8.4 weeks (range, 4-12 weeks). Most TREX patients who demonstrated recurrent exudative disease activity (17/24 [71%]) were unable to extend beyond their initial maximum extension interval. CONCLUSIONS: The TREX neovascular AMD management strategy used in this prospective, randomized, controlled trial resulted in visual and anatomic gains comparable with those obtained with monthly dosing.

Combination anti-VEGF and corticosteroid therapy for idiopathic retinal vasculitis, aneurysms, and neuroretinitis syndrome.

Vision loss associated with the idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome most commonly occurs from macular edema or complications related to neovascularization. The authors present a case of advanced IRVAN associated with a massive exudative response characterized by peripheral retinal telangiectasias, exudative retinal detachment, and macular edema with lipid maculopathy. The patient was managed successfully with visual acuity from hand motion to 20/150 using a combination of local corticosteroids, intravitreal bevacizumab, panretinal photocoagulation, and eventually pars plana vitrectomy for progressive vitreomacular traction. VEGF- and non-VEGF-mediated mechanisms appear to be involved in the pathogenesis of IRVAN given the efficacy of combination therapy. [ophthalmic surg lasers imaging retina. 2013;44:599-602.].

Retinal metastasis simulating cytomegalovirus retinitis.

A 62-year-old man with lung cancer presented with a 2-week history of decreased vision and clinical features of cytomegalovirus retinitis. The patient was empirically treated for viral retinitis, but microbiological testing of the vitreous fluid was negative. Based on the suspicion for retinal metastasis, the patient underwent pars plana vitrectomy with retinal biopsy. Surgical techniques included the use of a chandelier illumination to enable bimanual manipulation of the retinal tissue, creation a focal retinal detachment with a 41-gauge subretinal cannula, diathermy demarcation of the biopsy site, localized retinectomy with vertical scissors, endolaser, and long-acting gas tamponade. Histopathologic examination revealed sheets of tumor cells with pleomorphic nuclei and positive staining for cytokeratins consistent with metastatic adenocarcinoma. The patient subsequently underwent external beam radiation and was alive 10 months after presentation. This surgical technique may be valuable in select patients with retinal metastasis for diagnostic, therapeutic, and counseling purposes.

Multimodality diagnostic imaging in unilateral acute idiopathic maculopathy.

OBJECTIVE: To describe the clinical features and imaging characteristics in unilateral acute idiopathic maculopathy. METHODS: Retrospective review of 4 patients with a diagnosis of unilateral acute idiopathic maculopathy. Clinical characteristics (age, symptoms, Snellen visual acuity, and funduscopic features) and images from spectral-domain optical coherence tomography, fundus autofluorescence, fluorescein angiography, and indocyanine green angiography were analyzed. RESULTS: The median (range) age at presentation was 31 (27-52) years. The median (range) interval between symptom onset and presentation was 4 (1-20) weeks. Associated systemic findings included a viral prodrome (50%), orchitis (50%), hand-foot-mouth disease (25%), and positive coxsackievirus titers (50%). The median (range) visual acuity at initial examination was 20/400 (20/70 to 1/400), which improved to 20/30 (20/20 to 20/60) at final follow-up. The median (range) follow-up time was 8 (8-13) weeks. Early in the disease course, the central macula developed irregular, circular areas of white-gray discoloration. Following recovery, the macula had a stippled retinal pigment epithelium characterized by rarefaction and hyperplasia. Fluorescein angiography demonstrated irregular early hyperfluorescence and late subretinal hyperfluorescence. Spectral-domain optical coherence tomography showed a partially reversible disruption of the outer photoreceptor layer. Fundus autofluorescence initially revealed stippled autofluorescence that eventually became more hypoautofluorescent. Indocyanine green angiography showed "moth-eaten"-appearing choroidal vasculature, suggestive of choroidal inflammation. CONCLUSIONS: The imaging characteristics highlight the structural changes during the active and resolution phases of unilateral acute idiopathic maculopathy. The visual recovery correlates with structural changes and suggests that the pathogenesis involves inflammation of the inner choroid, retinal pigment epithelium, and outer photoreceptor complex that is partially reversible.

Negative electroretinograms in the pediatric and adult population.

Objective To assess the frequency of negative waveform electroretinograms (ERGs) in a tertiary referral center. Design Retrospective chart review. Participants All patients who had an ERG performed at the electrophysiology clinic at Emory University from January 1999 through March 2008 were included in the study. Methods Patients with b-wave amplitude ≤ a-wave amplitude during the dark-adapted bright flash recording, in at least one eye, were identified as having a "negative ERG". Clinical information, such as age, gender, symptoms, best corrected visual acuity, and diagnoses were recorded for these patients when available. Results A total of 1,837 patients underwent ERG testing during the study period. Of those, 73 patients had a negative ERG, for a frequency of 4.0%. Within the adult (≥ 18 years of age) and pediatric populations, the frequencies of a negative ERG were 2.5 and 7.2%, respectively. Among the 73 cases, negative ERGs were more common among male than female patients, 6.7% versus 1.8% (P < 0.0001). Negative ERGs were most common among male children and least common among female adults, 9.6% versus 1.1%, respectively, (P < 0.0001). Overall in this group of patients, the most common diagnoses associated with a negative ERG were congenital stationary night blindness (CSNB, n = 29) and X-linked retinoschisis (XLRS, n = 7). Conclusions The overall frequency of negative ERGs in this large retrospective review was 4.0%. Negative ERGs were most common among male children and least common among female adults. Despite the growing number of new diagnoses associated with negative ERGs, CSNB, and XLRS appear to be the most likely diagnoses for a pediatric patient who presents with a negative ERG.

Vitamin D insufficiency in diabetic retinopathy.

OBJECTIVE: To assess the relationship between vitamin D status and diabetic retinopathy. METHODS: A clinic-based, cross-sectional study was conducted at Emory University, Atlanta, Georgia. Overall, 221 patients were classified into 5 groups based on diabetes status and retinopathy findings: no diabetes or ocular disease (n = 47), no diabetes with ocular disease (n = 51), diabetes with no background diabetic retinopathy (n = 41), nonproliferative diabetic retinopathy (n = 40), and proliferative diabetic retinopathy (PDR) (n = 42). Patients with type 1 diabetes and those taking >1,000 IU of vitamin D daily were excluded from the analyses. Study subjects underwent dilated funduscopic examination and were tested for hemoglobin A1c, serum creatinine, and 25-hydroxyvitamin D [25(OH)D] levels between December 2009 and March 2010. RESULTS: Among the study groups, there was no statistically significant difference in age, race, sex, or multivitamin use. Patients with diabetes had lower 25(OH)D levels than did those without diabetes (22.9 ng/mL versus 30.3 ng/mL, respectively; P<.001). The mean 25(OH)D levels, stratified by group, were as follows: no diabetes or ocular disease = 31.9 ng/mL; no diabetes with ocular disease = 28.8 ng/mL; no background diabetic retinopathy = 24.3 ng/mL; nonproliferative diabetic retinopathy = 23.6 ng/mL; and PDR = 21.1 ng/mL. Univariate analysis of the 25(OH)D levels demonstrated statistically significant differences on the basis of study groups, race, body mass index, multivitamin use, hemoglobin A1c, serum creatinine level, and estimated glomerular filtration rate. In a multivariate linear regression model with all potential confounders, only multivitamin use remained significant (P<.001). CONCLUSION: This study suggests that patients with diabetes, especially those with PDR, have lower 25(OH)D levels than those without diabetes.

Imaging Retinal Vascular Changes in the Mouse Model of Oxygen-Induced Retinopathy.

PURPOSE: Oxygen-induced retinopathy in the mouse is the standard experimental model of retinopathy of prematurity. Assessment of the pathology involves in vitro analysis of retinal vaso-obliteration and retinal neovascularization. The authors studied the clinical features of oxygen-induced retinopathy in vivo using topical endoscopy fundus imaging (TEFI), in comparison to standard investigations, and evaluated a system for grading these features. METHODS: Postnatal day (P)7 mice were exposed to 75% oxygen for five days to induce retinopathy or maintained in room air as controls. Retinal vascular competence was graded against standard photographs by three masked graders. Retinal photographs were obtained at predetermined ages using TEFI. Postmortem, retinal vaso-obliteration was measured in whole mounts with labeled vasculature, and retinal neovascularization was quantified in hematoxylin- and eosin-stained ocular cross sections. RESULTS: Fundus photography by TEFI was possible from P15, when retinal vascular incompetence, including dilatation and tortuosity, was significant in mice with oxygen-induced retinopathy in comparison to controls. Vascular incompetence peaked in severity at P17 and persisted through P25. Comparison with in vitro analyses indicated that vascular changes were most severe after retinal avascularity had begun to decrease in area, and coincident with the maximum of retinal neovascularization. A weighted Fleiss-Cohen kappa indicated good intra- and interobserver agreement for a 5-point grading system. CONCLUSIONS: Topical endoscopy fundus imaging demonstrates retinal vascular incompetence in mice with oxygen-induced retinopathy. The technique complements standard postmortem analysis for following the course of the model. TRANSLATIONAL RELEVANCE: Topical endoscopy fundus imaging has application in the evaluation of novel biologic drugs for retinopathy of prematurity.

Logarithmic transformation of spectral-domain optical coherence tomography data in uveitis-associated macular edema.

PURPOSE: To determine the utility of logarithmic transformation of spectral-domain optical coherence tomography (logSD-OCT) retinal thickness data for assessment of clinically meaningful changes in uveitis-associated macular edema. METHODS: Patients with noninfectious uveitis-associated macular edema at our institution between August 2010 and March 2011 were identified. Only those with SD-OCT imaging were included. The clinical diagnoses, visual acuities, and central subfield thickness (CST) measurements were recorded. Logarithmic transformation of the retinal thickness was performed and frequency histograms plotted. A linear mixed-effects model of the logarithm minimum angle of resolution (logMAR) visual acuity on logSD-OCT was created to account for within-patient correlation among visits and between eyes. RESULTS: A total of 98 SD-OCT images from 34 patients were analyzed. The mean age at examination was 40 years (range, 11-69 years). Anatomic diagnoses included anterior/intermediate uveitis (23%), intermediate uveitis (21%), posterior uveitis (12%), and panuveitis (44%). LogSD-OCT data provided a more normal distribution than standard CST. Skewness and kurtosis of CST data were 1.04 and 0.37, respectively, and skewness and kurtosis of logSD-OCT data were 0.40 and -0.48, respectively. There was a positive correlation between logSD-OCT and logMAR visual acuity. Specifically, for each 0.1-unit increase in logSD-OCT, the logMAR visual acuities increased (worsened) by 0.082 units (95% CI: 0.057-0.107, P < 0.001). CONCLUSIONS: Logarithmic transformation of SD-OCT measurements provided a more normal distribution and positively correlated with logMAR visual acuity. This transformation of retinal thickness may be valuable for assessing clinically significant changes in SD-OCT measurements in future uveitis studies.