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BACKGROUND/AIMS: To identify clinical characteristics and factors associated with microcystic macular edema (MME) in patients with primary open-angle glaucoma (POAG). METHODS: We included 315 POAG eyes between 2010 and 2019 with good-quality macular volume scans that had reliable visual fields (VF) available within 6 months in this observational retrospective cohort study. Eyes with retinal pathologies except for epiretinal membrane (ERM) were excluded. The inner nuclear layer was qualitatively assessed for the presence of MME. Global mean deviation (MD) and Visual Field Index (VFI) decay rates, superior and inferior MD rates and pointwise total deviation rates of change were estimated with linear regression. Logistic regression was performed to identify baseline factors associated with the presence of MME and to determine whether MME is associated with progressive VF loss. RESULTS: 25 out of 315 eyes (7.9%) demonstrated MME. The average (±SD) age and MD in eyes with and without MME was 57.2 (±8.7) versus 62.0 (±9.9) years (p=0.02) and -9.8 (±5.7) versus -4.9 (±5.3) dB (p0.49). CONCLUSIONS: More severe glaucoma and younger age were associated with MME. MME was not associated with faster global VF decay in this cohort. MME may confound monitoring of glaucoma with full macular thickness.

Macular edema (ME), the accumulation of intraretinal fluid in the macula, is a common sight affecting sequelae of retinitis pigmentosa (RP). However, it is unclear why some patients develop ME, and others do not. This study aims to identify associations between clinical-genetic factors in RP with ME. Patients with clinically confirmed RP cases were identified from the inherited retinal disease database at a large tertiary referral academic center. Demographic and genetic testing findings were noted. Additionally, optical coherence tomography volume scans were graded using a validated grading system. One hundred and six patients (73.1%) were found to have ME in at least one eye (OD = 88, mean = 37.9%, OS = 98, mean = 31.7%). Structurally, the presence of epiretinal membrane (ERM) (p

PurposeTo determine if treatment with a photobiomodulation (PBM) device results in greater improvement in central subfield thickness (CST) than placebo in eyes with center-involved diabetic macular edema (CI-DME) and good vision.DesignPhase 2 randomized clinical trial.ParticipantsParticipants had CI-DME and visual acuity (VA) 20/25 or better in the study eye and were recruited from 23 clinical sites in the United States.MethodsOne eye of each participant was randomly assigned 1:1 to a 670-nm light-emitting PBM eye patch or an identical device emitting broad-spectrum white light at low power. Treatment was applied for 90 seconds twice daily for 4 months.Main outcome measuresChange in CST on spectral-domain OCT at 4 months.ResultsFrom April 2019 to February 2020, 135 adults were randomly assigned to either PBM (n = 69) or placebo (n = 66); median age was 62 years, 37% were women, and 82% were White. The median device compliance was 92% with PBM and 95% with placebo. OCT CST increased from baseline to 4 months by a mean (SD) of 13 (53) μm in PBM eyes and 15 (57) μm in placebo eyes, with the mean difference (95% confidence interval [CI]) being -2 (-20 to 16) μm (P = 0.84). CI-DME, based on DRCR Retina Network sex- and machine-based thresholds, was present in 61 (90%) PBM eyes and 57 (86%) placebo eyes at 4 months (adjusted odds ratio [95% CI] = 1.30 (0.44-3.83); P = 0.63). VA decreased by a mean (SD) of -0.2 (5.5) letters and -0.6 (4.6) letters in the PBM and placebo groups, respectively (difference [95% CI] = 0.4 (-1.3 to 2.0) letters; P = 0.64). There were 8 adverse events possibly related to the PBM device and 2 adverse events possibly related to the placebo device. None were serious.ConclusionsPBM as given in this study, although safe and well-tolerated, was not found to be effective for the treatment of CI-DME in eyes with good vision.

Purpose of reviewNearly 20 years ago, vascular endothelial growth factor (VEGF)inhibitors (VEGFi) were adapted from systemic use from antiangiogenesis roles to intravitreal uses. Initially bevacizumab a murine immunoglobulin was injected 'off label' as a treatment for diabetic macular edema and age-related macular degeneration. Throughout the following decade aflibercept and finally ranibizumab were adapted and obtained Food and Drug Administration approval for intravitreal use. Initially systemic absorption was thought to be quite low after intravitreal injections and was quoted as being 200-fold lower than levels postulated to induce significant VEGF inhibition. Pharmacodynamic studies obtained in 2014 and again in 2017 revealed significant systemic absorption and detectable VEGF inhibition, this has since been confirmed in multiple subsequent studies.Recent findingsA few case reports of renal dysfunction and glomerular disease related to VEGFi were initially identified. Mixed findings on effects on blood pressure were noted in studies. More recently, 32 cases of de-novo glomerular disease and/or proteinuria exacerbation were identified. New studies have corroborated increased blood pressure, proteinuria exacerbation in patients with pre-existing nephrotic syndrome, and systemic VEGF depletion. Further, the most common lesion of systemic VEGFi nephrotoxicity, thrombotic microangiopathy, has recently been reported by our group.SummaryWe will review the pharmacokinetic, translational, and epidemiological data that year upon year establish the finite-yet real risk of intravitreal VEGFi.

PurposeWe aimed to investigate non-exudative microcystoid macular abnormalities for visual and anatomical outcome in patients with retinal vein occlusion (RVO) with and without glaucomatous optic neuropathy (GON).MethodsMedical records of 124 eyes (105 patients) with RVO were reviewed and analyzed. Eyes demonstrating microcystoid macular abnormalities were divided into 2 groups, those with evidence of glaucoma (group A) and those without glaucoma (group B). Best-corrected visual acuity (BCVA), the prevalence and number of microcystoid macular abnormalities, and number of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections were compared at baseline and follow-up.ResultsSeventy-one out of 105 eyes (67.6%) with RVO displayed microcystoid macular abnormalities. Thirty-eight out of 71 eyes (53.5%) presented with concomitant glaucoma (group A), while the remaining 33 eyes (42.6%) had no history of glaucoma (group B). At the end of the follow-up period, mean BCVA was worse in group A versus group B (20/80 versus 20/40, respectively; p = .003). The mean number of anti-VEGF injections was 10.1 ± 9.2 in group A versus 5.9 ± 6.9 in group B (p = .03).ConclusionEyes with RVO and concomitant glaucoma exhibited a significantly higher number of microcystoid macular abnormalities and worse BCVA versus eyes with RVO without glaucoma.

PurposeTo identify clinical and anatomic factor-associated vision loss in eyes with treatment-naïve diabetic macular edema and good initial visual acuity.MethodsRetrospective cohort study after long-term history of eyes with untreated center-involving diabetic macular edema and baseline visual acuity ≥ 20/25 seen at the University of California, Davis Eye Center between March 2007 and March 2018. We collected characteristics including diabetes type, hemoglobin A1c, presence of visual symptoms, visual acuity, and diabetic retinopathy severity; and spectral-domain optical coherence tomography biomarkers including central subfield thickness, intraretinal cyst size, intraretinal hyperreflective foci, disorganization of retinal inner layers, and outer layer disruptions to determine factors associated with vision loss as defined by DRCR Protocol V as threshold for initiating aflibercept therapy.ResultsFifty-six eyes (48 patients) with untreated diabetic macular edema and mean baseline visual acuity of logMAR 0.05 ± 0.05 (Snellen 20/22) were followed for an average of 5.1 ± 3.3 years, with a median time to vision loss of 465 days (15 months). Older age (hazard ratio [HR] 1.04/year, P = 0.0195) and eyes with severe NPDR (HR 3.0, P = 0.0353) or proliferative diabetic retinopathy (HR 7.7, P = 0.0008) had a higher risk of a vision loss event. None of the spectral-domain optical coherence tomography biomarkers were associated with vision loss except central subfield thickness (HR 0.98, P = 0.0470) and cyst diameter (HR 1.0, P = 0.0094).ConclusionIn eyes with diabetic macular edema and good initial vision, those with older age and worse diabetic retinopathy severity should be monitored closely for prompt treatment initiation when vision loss occurs.

PurposeOptical coherence tomography (OCT) is widely used in the management of retinal pathologies, including age-related macular degeneration (AMD), diabetic macular edema (DME), and primary open-angle glaucoma (POAG). We used machine learning techniques to understand diagnostic performance gains from expanding macular OCT B-scans compared with foveal-only OCT B-scans for these conditions.MethodsElectronic medical records were extracted to obtain 61 B-scans per eye from patients with AMD, diabetic retinopathy, or POAG. We constructed deep neural networks and random forest ensembles and generated area under the receiver operating characteristic (AUROC) and area under the precision recall (AUPR) curves.ResultsAfter extracting 630,000 OCT images, we achieved improved AUROC and AUPR curves when comparing the central image (one B-scan) to all images (61 B-scans). The AUROC and AUPR points of diminishing return for diagnostic accuracy for macular OCT coverage were found to be within 2.75 to 4.00 mm (14-19 B-scans), 4.25 to 4.50 mm (20-21 B-scans), and 4.50 to 6.25 mm (21-28 B-scans) for AMD, DME, and POAG, respectively. All models with >0.25 mm of coverage had statistically significantly improved AUROC/AUPR curves for all diseases (P < 0.05).ConclusionsSystematically expanded macular coverage models demonstrated significant differences in total macular coverage required for improved diagnostic accuracy, with the largest macular area being relevant in POAG followed by DME and then AMD. These findings support our hypothesis that the extent of macular coverage by OCT imaging in the clinical setting, for any of the three major disorders, has a measurable impact on the functionality of artificial intelligence decision support.Translational relevanceWe used machine learning techniques to improve OCT imaging standards for common retinal disease diagnoses.

PURPOSE: To analyse the intraocular pressure rise after intravitreal dexamethasone implant (Ozurdex) amongst different geographic populations. METHODS: The medical charts of 294 dexamethasone implants between February 2011 and 2017 were reviewed retrospectively. South Asian (India), White (Europe, US and Israel) Latino (Argentina and Brazil) patient data was included in the study. Ocular hypertension (OHT) was defined as intraocular pressure of >25 mmHg or an increase of at least 10 mmHg from baseline. The main indications for treatment were diabetic macular edema (ME) (65.6%), retinal vein occlusion (26.5%), uveitis (7.8%). RESULTS: Amongst 294 intravitreal implants, ocular hypertension (>25 mmHg) was recorded in 0, 8 and 9.5% in White, Latino, and South Asian groups, respectively. However, IOP > 20 mmHg was recorded in 14%, 28% and 27% in White, Latino, and South Asian groups, respectively. Incidence of very high IOP (>35 mmHg) was lower in all geographical groups. It was 3% in Latino followed by 2% in South Asian group. CONCLUSION: Latino and South Asian groups have higher IOP rise compared to White population. Most patients with elevated IOP fluctuate between 20-25 mmHg.

PurposeTo evaluate the management and long-term outcomes of patients with diabetic macular oedema (DMO) and good initial visual acuity in real-world settings.MethodsWe reviewed 122 eyes of 100 patients with treatment-naive DMO and initial best-corrected visual acuity (BCVA) of 20/25 or better. We assessed clinical characteristics, logMAR BCVA, central subfield thickness (CST), cumulative intravitreal injections and laser treatments at yearly intervals, and characteristics at time of initial treatment. Linear mixed effects models were used to identify predictors of visual outcomes.ResultsAt presentation, mean BCVA was 0.057 ± 0.048 logMAR (Snellen 20/23) and mean CST was 288 ± 57 μm. After a median follow-up of 3 years, 51% of eyes underwent treatment. More eyes underwent intravitreal injection as initial treatment (54%), but lasers were initiated at an earlier time and at better BCVA. Final BCVA was associated with better BCVA (P

PurposeTo analyse the intraocular pressure rise after intravitreal dexamethasone implant (Ozurdex) amongst different geographic populations.MethodsThe medical charts of 294 dexamethasone implants between February 2011 and 2017 were reviewed retrospectively. South Asian (India), White (Europe, US and Israel) Latino (Argentina and Brazil) patient data was included in the study. Ocular hypertension (OHT) was defined as intraocular pressure of >25 mmHg or an increase of at least 10 mmHg from baseline. The main indications for treatment were diabetic macular edema (ME) (65.6%), retinal vein occlusion (26.5%), uveitis (7.8%).ResultsAmongst 294 intravitreal implants, ocular hypertension (>25 mmHg) was recorded in 0, 8 and 9.5% in White, Latino, and South Asian groups, respectively. However, IOP > 20 mmHg was recorded in 14%, 28% and 27% in White, Latino, and South Asian groups, respectively. Incidence of very high IOP (>35 mmHg) was lower in all geographical groups. It was 3% in Latino followed by 2% in South Asian group.ConclusionLatino and South Asian groups have higher IOP rise compared to White population. Most patients with elevated IOP fluctuate between 20-25 mmHg.

PurposeTo determine clear-cut distinctions between tractional and exudative intraretinal cystoid spaces subtypes.DesignRetrospective, multicenter, observational case series.MethodsA cohort of patients diagnosed with intraretinal cystoid spaces and imaged with optical coherence tomography (OCT), fluorescein angiography (FA), blue fundus autofluorescence (BFAF), en face OCT, and OCT angiography (OCT-A) was included in the study. All images were qualitatively and quantitatively evaluated.ResultsIn this study were included 72 eyes of 69 patients. Exudative intraretinal cystoid spaces (36/72 eyes, 50%) displayed a "petaloid" morphology as seen with en face OCT, FA, and BFAF. Tractional intraretinal cystoid spaces (24/72 eyes, 33.3%), displayed a radial "spoke-wheel" en face OCT pattern. There was no leakage with FA and BFAF did not reveal specific patterns. Eyes with full-thickness macular hole (FTMH, 12/72 eyes, 16.7%) displayed a "sunflower" en face OCT appearance. FTMH showed OCT, OCT-A, and BFAF features of both exudative and tractional cystoid spaces, but without any FA leakage. Inner nuclear layer (INL) thickness was significantly lower in tractional cystoid spaces (P < .001). There were a greater number of INL cystoid spaces in both the exudative and FTMH subgroups (P = .001). The surface area of INL cystoid spaces was significantly lower in the tractional subgroup (P < .001). There was a significant reduction of the microvascular density in eyes with exudative vs tractional (P = .002) and FTMH (P < .001) subgroups.ConclusionsExudative and tractional intraretinal cystoid spaces displayed characteristic multimodal imaging features and they may represent 2 different pathologic conditions with equally different clinical implications.

Diabetic retinopathy (DR) is the most common cause of blindness for individuals under the age of 65. This loss of vision can be due to ischemia, neovascularization, and/or diabetic macular edema, which are caused by breakdown of the blood-retina barrier at the level of the retinal pigment epithelium (RPE) and inner retinal vasculature. The prevalence of diabetes and its complications differ between Caucasian-Americans and certain minority populations, such as African-Americans and Asian-Americans. Individuals can be classified by their mitochondrial haplogroups, which are collections of single nucleotide polymorphisms (SNPs) in mitochondrial DNA (mtDNA) representing ancient geographic origins of populations. In this study, we compared the responses of diabetic human RPE cybrids, cell lines containing identical nuclei but mitochondria from either European (maternal European) or maternal African or Asian individuals, to hypoxia and high glucose levels. The African and Asian diabetic ([Afr+Asi]/DM) cybrids showed (1) resistance to both hyperglycemic and hypoxic stresses; (2) downregulation of pro-apoptotic indicator BAX; (3) upregulation of DNA methylation genes, such as DNMT3A and DNMT3B; and (4) resistance to DNA demethylation by the methylation inhibitor 5-Aza-2'-deoxycytidine (5-Aza-dC) compared to European diabetic (Euro/DM) cybrids. Our findings suggest that mitochondria from African and Asian diabetic subjects possess a "metabolic memory" that confers resistance against hyperglycemia, hypoxia, and demethylation, and that this "metabolic memory" can be transferred into the RPE cybrid cell lines in vitro.

Center-involved diabetic macular edema (ci-DME) is a major cause of vision loss. Although the gold standard for diagnosis involves 3D imaging, 2D imaging by fundus photography is usually used in screening settings, resulting in high false-positive and false-negative calls. To address this, we train a deep learning model to predict ci-DME from fundus photographs, with an ROC-AUC of 0.89 (95% CI: 0.87-0.91), corresponding to 85% sensitivity at 80% specificity. In comparison, retinal specialists have similar sensitivities (82-85%), but only half the specificity (45-50%, p

PurposeTo evaluate spectral-domain (SD)-OCT features associated with baseline vision and visual outcomes in the prospective, multicenter Study Evaluating Dosing Regimens for Treatment with Intravitreal Ranibizumab Injections in Subjects with Macular Edema following Retinal Vein Occlusion (SHORE).DesignPost hoc analysis of prospective clinical trial data.ParticipantsTwo hundred two participants in the 15-month, phase 4 SHORE study comparing monthly versus pro re nata ranibizumab after 7 monthly doses in eyes with retinal vein occlusion (RVO) with macular edema.MethodsBaseline SD-OCT images were assessed for (1) central subfield thickness (CST); (2) presence of vitreomacular adhesion, vitreomacular traction, or epiretinal membrane; (3) presence, location, and amount of intraretinal fluid or subretinal fluid (SRF); (4) presence, location, and amount of hyperreflective foci (HF); (5) disorganization of retinal inner layers (DRIL); and (6) disruption of external limiting membrane (ELM), ellipsoid zone (EZ), and interdigitation zone (IZ). Univariate and multivariate regression analyses were performed to evaluate the association of these features with baseline best-corrected visual acuity (BCVA) and change in BCVA after 7 monthly ranibizumab injections.Main outcome measuresAssociation of SD-OCT features with baseline BCVA and change in BCVA after 7 monthly ranibizumab injections.ResultsBefore therapy, worse baseline BCVA was associated with ERM presence (P = 0.0045), thicker SRF (P = 0.0006), larger intraretinal cysts (P = 0.0015), and higher percentage of DRIL (P < 0.0001), percentage of ELM disruption (P < 0.0001), percentage of EZ disruption (P = 0.0003), and percentage of IZ disruption (P = 0.0018). In multivariate models, only percentage of ELM disruption independently impacted baseline BCVA (P < 0.0001). After 7 monthly ranibizumab injections, mean BCVA improved by 18.3±12.6 Early Treatment Diabetic Retinopathy Study letters in treated eyes. The only factors independently associated with BCVA gain after 7 monthly ranibizumab treatments were younger age (P < 0.0001) and worse baseline BCVA (P < 0.0001).ConclusionsAlthough SD-OCT features may be associated with presenting vision in eyes with macular edema and RVO, most eyes treated with ranibizumab achieve substantial vision gains, and only older age and better baseline BCVA limited visual improvements.

PurposeTo evaluate outcomes in patients with hypotony treated with intravitreal dexamethasone implant (Ozurdex).DesignRetrospective cohort study.ParticipantsThirteen patients (15 eyes) that received a total of 99 dexamethasone implant injections on occasions at which the intraocular pressure was low, meeting the definition of statistical hypotony.MethodsThe medical records of 13 patients (15 consecutive eyes) receiving 1 or more intravitreal dexamethasone implants between December 2014 and April 2017 were reviewed retrospectively. Hypotony was defined as intraocular pressure less than 6.5 mmHg. The indications for intravitreal dexamethasone implant injection were intermediate or posterior uveitis (86.7%), diabetic macular edema (13.3%), and/or cystoid macular edema (6.7%).Main outcome measuresThe primary outcome measures were safety outcomes and best visual acuity within 6 months of the final intravitreal dexamethasone implant injection in a hypotonous eye.ResultsIn 15 eyes (13 patients), 99 injections were administered to eyes under circumstances of hypotony. Uveitic cystoid macular edema or diabetic macular edema was reduced after treatment in all cases. No complications were noted during the injection procedure. Three complications were noted in 2 patients after injection. Pseudophakodonesis and mild vitreous hemorrhage immediately after injection were noted in 1 patient, and a case of delayed-onset vitreous hemorrhage with pigment release was noted in another. All 3 complications resolved without intervention. The primary end point of this study-mean visual acuity-was stable over the follow-up period. In patients with hypotony whose intraocular pressure normalized during the follow-up period, this was attributable to management of glaucoma surgery-related complications rather than an effect of the intravitreal dexamethasone implant.ConclusionsIntravitreal dexamethasone implant injection is a reasonable treatment option for patients with comorbid hypotony in whom clinical findings warrant treatment with a sustained-delivery intravitreal steroid implant. Further studies, including imaging of zonules before and after intravitreal dexamethasone implant injection in a hypotonous eye, could help define risks to intraocular lens stability with this procedure.

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Background: Inherited retinal dystrophies are a leading cause of irreversible blindness in children in the United States. Topical carbonic anhydrase inhibitors have improved central vision and cystoid macular edema in patients with retinal dystrophies, but few studies have assessed their efficacy in children. Materials and Methods: A retrospective chart review was performed with Institutional Review Board approval to identify pediatric patients with inherited retinal dystrophies who received topical brinzolamide at a single university center between 2008 and 2015. Serial visual acuity and central macular thicknesses were compared to assess the efficacy of brinzolamide. Results: Seven subjects were identified who met the inclusion criteria. Four had juvenile X-linked retinoschisis, two had retinitis pigmentosa, and one had Leber congenital amaurosis. All were prescribed brinzolamide thrice daily; however, one patient was completely non-compliant. Four of the six treated patients exhibited a mild decrease in central macular thickness in both eyes during the study with all six treated patients having significantly improved vision at the first endpoint, 33.2 ± 8.2 months after treatment initiation. For treated patients, average visual acuity (LogMAR) ± standard error of the mean improved from 0.5 ± 0.04 pre-treatment to 0.3 ± 0.1 at the second endpoint, 50.2 ± 7.3 months after treatment initiation. Conclusions: Mild anatomic improvement of macular cysts was seen in pediatric patients using brinzolamide. Visual acuity improvement occurred even without significant reduction in macular cysts. Further studies are needed to determine whether the beneficial effects of carbonic anhydrase inhibitors are sustained in children with inherited retinal degenerations.

PurposeTo evaluate the comparative effectiveness of 3 regional corticosteroid injections for uveitic macular edema (ME): periocular triamcinolone acetonide (PTA), intravitreal triamcinolone acetonide (ITA), and the intravitreal dexamethasone implant (IDI).DesignMulticenter, randomized clinical trial.ParticipantsPatients with uveitic ME.MethodsPatients were randomized 1:1:1 to receive 1 of the 3 therapies. Patients with bilateral ME were assigned the same treatment for both eyes.Main outcome measuresThe primary outcome was the proportion of baseline (PropBL) central subfield thickness (CST) at 8 weeks (CST at 8 weeks/CST at baseline) assessed with OCT by masked readers. Secondary outcomes included ≥20% improvement and resolution of ME, best-corrected visual acuity (BCVA), and intraocular pressure (IOP) events over 24 weeks.ResultsAll treatment groups demonstrated improved CST during follow-up. At 8 weeks, each group had clinically meaningful reductions in CST relative to baseline (PropBL: 0.77, 0.61, and 0.54, respectively, which translates to reductions of 23%, 39%, and 46% for PTA, ITA, and IDI, respectively). Intravitreal triamcinolone acetonide (PropBL ITA/PropBL PTA, hazard ratio [HR], 0.79; 99.87% confidence interval [CI], 0.65-0.96) and IDI (PropBL IDI/PropBL PTA, HR, 0.69; 99.87% CI, 0.56-0.86) had larger reductions in CST than PTA (P < 0.0001). Intravitreal dexamethasone implant was noninferior to ITA at 8 weeks (PropBL IDI/PropBL ITA, HR, 0.88; 99.87% CI, 0.71-1.08). Both ITA and IDI treatments also were superior to PTA treatment in improving and resolving uveitic ME. All treatment groups demonstrated BCVA improvement throughout follow-up. Both ITA and IDI groups had improvements in BCVA that was 5 letters greater than in the PTA group at 8 weeks (P < 0.004). The risk of having IOP ≥24 mmHg was higher in the intravitreal treatment groups compared with the periocular group (HR, 1.83; 95% CI, 0.91-3.65 and HR, 2.52; 95% CI, 1.29-4.91 for ITA and IDI, respectively); however, there was no significant difference between the 2 intravitreal treatment groups.ConclusionsIntravitreal triamcinolone acetonide and the IDI were superior to PTA for treating uveitic ME with modest increases in the risk of IOP elevation. This risk did not differ significantly between intravitreal treatments.

PurposeTo evaluate the integrity of outer retina layers after resolution of central involved diabetic macular edema (DME) and to demonstrate the effect of various baseline factors for the final vision and final external limiting membrane (ELM) integrity.MethodsFifty-nine eyes of 48 patients with resolved DME were included. Several optical coherence tomography parameters including central subfield thickness, maximum foveal thickness, foveal center point thickness, and the extent of the ellipsoidal (ISe) layer and ELM damage were assessed at the time of DME and after resolution of DME. Eyes having laser scars near the fovea were excluded. Final visual acuity was classified as good (Snellen≥20/40, logarithm of the minimum angle of resolution ≤0.3) or impaired (Snellen 0.3) for the logistic regression analysis. Zero Inflated Poison Regression model was used to find the best predictors for post-treatment ELM damage.ResultsExternal limiting membrane and inner segment ellipsoidal band layers were disrupted in 16 eyes (27.2%) and 21 eyes (35.5%) at the final visit, respectively. Baseline ELM damage (p=0.001), baseline impaired vision (p= 0.013), and the most recent glycosylated hemoglobin level (p=0.018) were the best set of parameters for having impaired final visual acuity. Baseline vision, severity of diabetic retinopathy, absence of intravitreal injection, central subfield thickness, and history of extrafoveal macular laser (not within 1 mm of fovea) (p

PurposeTo describe the design and baseline characteristics of participants in the Study of COmparative Treatments for REtinal Vein Occlusion 2 (SCORE2) and to compare with cohorts from other retinal vein occlusion trials.DesignPhase III prospective, multicenter, randomized clinical trial designed to assess whether intravitreal bevacizumab is noninferior to intravitreal aflibercept for treatment of decreased vision attributable to macular edema associated with central retinal vein occlusion (CRVO) or hemiretinal vein occlusion (HRVO).ParticipantsTotal of 362 participants: 307 with CRVO and 55 with HRVO.MethodsDemographic and study eye characteristics are summarized and compared between CRVO and HRVO study participants.Main outcome measuresBaseline ophthalmic characteristics, including visual acuity and retinal thickness, and medical history characteristics, including hypertension, diabetes mellitus, and coronary artery disease.ResultsThe mean age of participants was 69 years, 76% of participants were white, and 90% were non-Hispanic. There was a racial disparity with respect to disease type, with 38% of HRVO patients being black compared with 11% of CRVO patients (P value adjusted for multiple testing = 0.0001). This is similar to findings from the previous SCORE Study. Comorbidities included hypertension (77%), diabetes mellitus (31%), and coronary artery disease (15%). At baseline, mean visual acuity letter score was 50 (20/100) (range, 19-73 [20/400 to 20/40]), mean optical coherence tomography (OCT)-measured central subfield thickness was 678 μm (range, 300-1203 μm), and mean number of months from diagnosis of macular edema to randomization was 6 (range, 0-104 months). One hundred twenty (33%) SCORE2 participants had been treated previously with anti-vascular endothelial growth factor (anti-VEGF) therapy, with these participants having baseline visual acuity letter score and OCT-measured central subfield thickness similar to those without prior anti-VEGF treatment, but longer mean duration of macular edema before randomization (18 months vs. 1 month for those without prior anti-VEGF treatment; P < 0.0001).ConclusionsThe SCORE2 cohort is a heterogeneous population, including both CRVO and HRVO eyes and both treatment-naïve eyes and eyes treated previously with anti-VEGF, which will allow study results to have broad applicability to CRVO and HRVO patients receiving treatment for macular edema. Similarities of the baseline characteristics of the SCORE2 population to other CRVO trial cohorts will allow meaningful comparisons of outcome results across trials.

Corticosteroids are unique in that they are the one class of agents that acts upon most of the multiple processes in the pathophysiology of macular edema. Corticosteroids are capable of inhibiting prostaglandin and leukotriene synthesis as well as interfering with intercellular adhesion molecule-1 (ICAM-1), interleukin-6, VEGF-A, and stromal cell derived factor-1 pathways. Triamcinolone, dexamethasone, and fluocinolone have been extensively used in the treatment of retinal and choroidal vascular diseases. Sustained release implants of steroids have reduced the burden of repeated intravitreal injections necessary in most of the retinal diseases. Complement factors play an important role in the pathogenesis of age-related macular degeneration (AMD). Inhibitors of complement could provide a breakthrough in the treatment of dry AMD. Complement factor inhibitors, such as POT-4, lampalizumab, and eculizumab, have been tested in clinical trials for dry AMD with promising results. However, results of phase 3 trials are awaited.

Background: Optimal regimen using intravitreal aflibercept injections for diabetic macular edema (DME) in clinical practice remains to be elucidated. The purpose of this study is to evaluate a treat-and-extend (TAE) approach using intravitreal aflibercept in participants with center-involved DME. Methods: A 52-week open-label, prospective, multicenter, interventional study was conducted between August 2015 and November 2017 in Taiwan. Adults with diabetes mellitus and center-involved DME who have best-corrected visual acuity (BCVA) of 73 to 24 Early Treatment Diabetic Retinopathy Study letters and central retinal thickness (CRT) >300 µm were included. Participants received five monthly loading doses of 2 mg intravitreal aflibercept, followed by a TAE regimen with a four-week increment/decrement interval over 48 weeks; the maximum interval was 12 weeks. Main outcomes included changes in BCVA and CRT from baseline to week 52, additional anatomical outcomes, and treatment burden parameters. Results: Forty-five participants with mean (SD) age of 63.7 (8.3) years were analyzed. At baseline, mean (SD) BCVA and CRT were 58.3 (11.9) letters and 434.4 (116.8) µm, respectively. Changes from baseline in BCVA and CRT were +8.3 (9.3) letters and -138.2 (150.0) µm (both p < 0.001) at week 52, respectively. In addition, 22% (10/45) of patients gained =15 letters, 14% (6/44) of participants achieved =2-level improvement in diabetic retinopathy severity, and 51% (23/45) demonstrated dry retina at week 52 compared with 13% (6/45) at baseline. In total, 87% (39/45) of patients reached disease stability, entering TAE at week 20. Subsequently, 89% (40/45) of patients reached maximum interval at week 52. Mean (SD) number of injections was 7.7 (1.5) over a period of 52 weeks. Conclusion: This straightforward and practical TAE regimen using intravitreal aflibercept injections resulted in favorable clinical outcomes with minimal treatment burden for DME at week 52. [ABSTRACT FROM AUTHOR]

Nonsteroidal antiinflammatory drugs (NSAIDs) have become an important adjunctive tool for surgeons performing routine and complicated cataract surgery. These medications have been found to reduce pain, prevent intraoperative miosis, modulate postoperative inflammation, and reduce the incidence of cystoid macular edema (CME). Whether used alone, synergistically with steroids, or for specific high-risk eyes prone to the development of CME, the effectiveness of these medications is compelling. This review describes the potential preoperative, intraoperative, and postoperative uses of NSAIDs, including the potency, indications and treatment paradigms and adverse effects and contraindications. A thorough understanding of these issues will help surgeons maximize the therapeutic benefits of these agents and improve surgical outcomes.Financial disclosureProprietary or commercial disclosures are listed after the references.

PurposeMacular pigment, composed of lutein, zeaxanthin, and meso-zeaxanthin, is postulated to protect against age-related macular degeneration, likely because of filtering blue light and its antioxidant properties. Macular pigment optical density (MPOD) is reported to be associated with macular function evaluated by visual acuity and multifocal electroretinogram. Given the importance of macular pigment, reliable and accurate measurement methods are important. The main purpose of this study is to determine the reproducibility of MPOD measurement by two-wavelength autofluorescence method using scanning laser ophthalmoscopy.MethodsSixty-eight eyes of 39 persons were enrolled in the study, including 11 normal eyes, 16 eyes with wet age-related macular degeneration, 16 eyes with dry age-related macular degeneration, 11 eyes with macular edema due to diabetic mellitus, branch retinal vein occlusion or macular telangiectasia, and 14 eyes with tractional maculopathy, including vitreomacular traction, epiretinal membrane, or macular hole. MPOD was measured with a two-wavelength (488 and 514 nm) autofluorescence method with the Spectralis HRA + OCT after pupil dilation. The measurement was repeated for each eye 10 minutes later. The analysis of variance and Bland-Altman plot were used to assess the reproducibility between the two measurements.ResultsThe mean MPOD at eccentricities of 1° and 2° was 0.36 ± 0.17 (range: 0.04-0.69) and 0.15 ± 0.08 (range: -0.03 to 0.35) for the first measurement and 0.35 ± 0.17 (range: 0.02-0.68) and 0.15 ± 0.08 (range: -0.01 to 0.33) for the second measurement, respectively. The difference between the 2 measurements was not statistically significant, and the Bland-Altman plot showed 7.4% and 5.9% points outside the 95% limits of agreement, indicating an overall excellent reproducibility. Similarly, there is no significant difference between the first and second measurements of MPOD volume within eccentricities of 1°, 2°, and 6° radius, and the Bland-Altman plot showed 8.8%, 2.9%, and 4.4% points outside the 95% limits of agreement, respectively. The data for the reproducibility did not differ significantly among the various disease and normal eyes.ConclusionUnder routine examination conditions with pupil dilation, MPOD measurement by two-wavelength autofluorescence method showed a high reproducibility.

PurposeTo evaluate the outcomes of different types of treatment of chronic cystoid macular edema (CME) after pars plana vitrectomy.MethodsRetrospective review of eyes that developed chronic CME after pars plana vitrectomy treated with intravitreal triamcinolone acetonide (TCA) with or without the addition of anti-vascular endothelial growth factor.ResultsThirty-nine eyes of 37 patients were included, with a median duration between pars plana vitrectomy and onset of CME of 5 months (interquartile range, 3-12). In most eyes (66.7%), the main indication for surgery was for vitreomacular interface disorders, such as epiretinal membrane, vitreomacular traction, and macular hole. With intravitreal TCA, there was a significant decrease in central foveal thickness at 3, 6, and 12 months, compared with baseline (P = 0.0171, 0.0401, and 0.0024, respectively). A significant gain in vision was noted at 1 month compared with baseline (P = 0.0169), but this was not sustained at 3, 6, and 12 months (P = 0.4862, 0.9098, and 0.4312, respectively). The addition of bevacizumab to TCA did not provide any additional benefit for central foveal thickness and visual acuity. Thirty-two eyes (82.1%) were started on prophylactic antiglaucoma drops 2 weeks after a TCA injection, and no eye needed laser or surgery to control intraocular pressure.ConclusionChronic CME after pars plana vitrectomy is recurrent and difficult to treat. Intravitreal TCA is effective in reducing CME, but there was only short-term visual acuity improvement even with continued reduction of central foveal thickness. Intraocular pressure did not significantly rise with the use of prophylactic antiglaucoma drops even with repeated injections.

Corticosteroids are unique in that they are the one class of agents that acts upon most of the multiple processes in the pathophysiology of macular edema. Corticosteroids are capable of inhibiting prostaglandin and leukotriene synthesis as well as interfering with intercellular adhesion molecule-1 (ICAM-1), interleukin-6, VEGF-A, and stromal cell derived factor-1 pathways. Triamcinolone, dexamethasone, and fluocinolone have been extensively used in the treatment of retinal and choroidal vascular diseases. Sustained release implants of steroids have reduced the burden of repeated intravitreal injections necessary in most of the retinal diseases. Complement factors play an important role in the pathogenesis of age-related macular degeneration (AMD). Inhibitors of complement could provide a breakthrough in the treatment of dry AMD. Complement factor inhibitors, such as POT-4, lampalizumab, and eculizumab, have been tested in clinical trials for dry AMD with promising results. However, results of phase 3 trials are awaited.

BackgroundDexamethasone intravitreal implant 0.7 mg (DEX 0.7) was approved for treatment of diabetic macular edema (DME) after demonstration of its efficacy and safety in the MEAD registration trials. We performed subgroup analysis of MEAD study results to evaluate the efficacy and safety of DEX 0.7 treatment in patients with previously treated DME.MethodsThree-year, randomized, sham-controlled phase 3 study in patients with DME, best-corrected visual acuity (BCVA) of 34-68 Early Treatment Diabetic Retinopathy Study letters (20/200-20/50 Snellen equivalent), and central retinal thickness (CRT) ≥ 300 μm measured by time-domain optical coherence tomography. Patients were randomized to 1 of 2 doses of DEX (0.7 mg or 0.35 mg), or to sham procedure, with retreatment no more than every 6 months. The primary endpoint was ≥ 15-letter gain in BCVA at study end. Average change in BCVA and CRT from baseline during the study (area-under-the-curve approach) and adverse events were also evaluated. The present subgroup analysis evaluated outcomes in patients randomized to DEX 0.7 (marketed dose) or sham based on prior treatment for DME at study entry.ResultsBaseline characteristics of previously treated DEX 0.7 (n = 247) and sham (n = 261) patients were similar. In the previously treated subgroup, mean number of treatments over 3 years was 4.1 for DEX 0.7 and 3.2 for sham, 21.5% of DEX 0.7 patients versus 11.1 % of sham had ≥ 15-letter BCVA gain from baseline at study end (P = 0.002), mean average BCVA change from baseline was +3.2 letters with DEX 0.7 versus +1.5 letters with sham (P = 0.024), and mean average CRT change from baseline was -126.1 μm with DEX 0.7 versus -39.0 μm with sham (P

PurposeTo evaluate the 2-year outcomes of uveitic macular edema.DesignLongitudinal follow-up of a randomized cohort.ParticipantsAt baseline, 148 eyes of 117 patients enrolled in the Multicenter Uveitis Steroid Treatment (MUST) Trial had macular edema, and 134 eyes of 108 patients completed 2-year follow-up.MethodsPatients enrolled in the study were randomized to either systemic immunosuppression or intravitreal fluocinolone acetonide implant therapy. Macular edema was defined as thickening of the retina (center point thickness≥240 μm) on time-domain optical coherence tomography (OCT) of macula.Main outcome measuresImprovement in macular edema (≥20% reduction in central point thickness on OCT), resolution of macular edema (normalization of thickness on OCT), and best-corrected visual acuity (BCVA).ResultsBetween randomization and 2-years' follow-up, 62% and 25% of eyes in the systemic and implant groups, respectively, received at least 1 supplemental regional corticosteroid injection. By 2-years' follow-up, macular edema improved in 71% of eyes and resolved in 60%. There were no differences between treatment groups in the proportion of eyes with macular edema improving (systemic therapy vs. implant, 65% vs. 77%; P=0.20) and resolving (52% vs. 68%; P=0.28), but eyes randomized to implant had more improvement in macular thickness (median decrease of 180 vs. 109 μm in the systemic therapy group; P=0.04). Eyes with baseline fluorescein angiographic leakage were more likely to improve than those without (76% vs. 58%; P=0.03). Overall, there was a mean 5-letter (1 line) improvement in BCVA at 2 years. Mean changes in BCVA from baseline at 2 years by macular edema response status were: resolution, +10 letters; improvement without resolution, +10 letters (P=0.92); little to no change, 6 letters (P=0.19); and worsening, -16 letters (worsening acuity; P=0.0003).ConclusionsAbout two thirds of eyes with uveitic macular edema were observed to experience improvement in the edema and visual acuity with implant or systemic treatment. Fluocinolone acetonide implant therapy was associated with a greater quantitative improvement in thickness. Fluorescein angiography leakage was associated with a greater likelihood of improvement in macular edema.

PurposeTo analyze intraocular pressure (IOP) response after 20-mg decanted intravitreal triamcinolone acetonide followed by early prophylactic IOP-lowering therapy.MethodsOverall, IOP results of 120 high-dose decanted intravitreal triamcinolone acetonide injections from 58 nonglaucomatous patients with macular edema, with antiglaucoma therapy prescribed from Week 1 regardless of baseline IOP were retrospectively reviewed.ResultsIn cases of consistent compliance with IOP-lowering drugs (79.2%), IOP increased by 2 mmHg at 4 months (P = 0.300) and returned to baseline at 6 months. In cases of noncompliance (20.8%), IOP increased by 7 mmHg at 1 month (P < 0.001) and returned to baseline after starting treatment. Multivariate regression analysis showed that nonvitrectomized eyes and noncompliance with IOP-lowering drugs were independent predictors of increase in IOP greater than 21 mmHg (P = 0.0098 and P = 0.0019, respectively). Nonvitrectomized eyes had a 46% greater chance to experience increase in IOP compared with vitrectomized ones. Poor compliance with IOP-lowering drugs lead to a 45% greater likelihood of experiencing increase in IOP compared with compliant patients. Multiple injections were not associated with the increased risk for increase in IOP greater than 21 mmHg (P = 0.273). Of 120 cases, 2 eyes (1.7%) developed uncontrolled IOP and required glaucoma surgery by 4 months, with good final IOP outcome.ConclusionTwenty milligram decanted intravitreal triamcinolone acetonide can be safely used to treat macular edema in nonglaucomatous patients; IOP elevation can be adequately controlled with prophylactic antiglaucoma drugs. Noncompliance with prophylactic therapy creates an early spike in IOP, and vitreous status can significantly impact increase in IOP. Compliance with IOP-lowering drugs should be stressed to patients receiving high-dose intravitreal triamcinolone acetonide especially in cases of nonvitrectomized eyes.

PurposeTo determine the effect of anti-vascular endothelial growth factor (VEGF) therapy on choroidal thickness in eyes with diabetic macular edema (DME).DesignA retrospective, cohort analysis of 59 eyes from 59 patients with DME without prior anti-VEGF therapy.MethodsChoroidal thickness was measured using semiautomated segmentation of enhanced depth imaging optical coherence tomography images at 0.5-mm intervals from 2.5 mm nasal to 2.5 mm temporal to the fovea. Changes in choroidal thickness with and without anti-VEGF treatment over 6 months were compared. Best-corrected visual acuity and central foveal thickness were analyzed to evaluate the association of choroidal thickness with functional and anatomic outcomes.ResultsOf the 59 eyes with DME, 26 eyes were observed without treatment, whereas 33 underwent intravitreal anti-VEGF therapy (mean number of injections, 2.73) over 6 months. In untreated eyes, there was no significant change in best-corrected visual acuity (P = .098), central foveal thickness (P = .472), or choroidal thickness at all measurements along the macula (P = .057 at the fovea). In eyes treated with anti-VEGF injections, choroidal thickness decreased significantly at the fovea (246.6 to 224.8 μm; P < .001) and at 0.5 mm nasal (240.9 to 221.9 μm; P = .002) and 0.5 mm temporal (249.3 to 224.8 μm; P = .011) to the fovea. The decrease in subfoveal choroidal thickness after anti-VEGF treatment was not associated with the cumulative number of anti-VEGF injections (R(2) = 0.031; P = .327) or to changes in best-corrected visual acuity (R(2) = 0.017; P = .470) or central foveal thickness (R(2) = 0.040; P = .263).ConclusionsCentral choroidal thickness decreases after anti-VEGF therapy for DME after 6 months, but may not be associated with functional or anatomic outcomes in eyes with DME.

ObjectiveTo compare the relative effectiveness of methotrexate and mycophenolate mofetil for noninfectious intermediate uveitis, posterior uveitis, or panuveitis.DesignMulticenter, block-randomized, observer-masked clinical trial.ParticipantsEighty patients with noninfectious intermediate, posterior, or panuveitis requiring corticosteroid-sparing therapy at Aravind Eye Hospitals in Madurai and Coimbatore, India.InterventionPatients were randomized to receive 25 mg weekly oral methotrexate or 1 g twice daily oral mycophenolate mofetil and were monitored monthly for 6 months. Oral prednisone and topical corticosteroids were tapered.Main outcome measuresMasked examiners assessed the primary outcome of treatment success, defined by achieving the following at 5 and 6 months: (1) ≤0.5+ anterior chamber cells, ≤0.5+ vitreous cells, ≤0.5+ vitreous haze and no active retinal/choroidal lesions in both eyes, (2) ≤10 mg of prednisone and ≤2 drops of prednisolone acetate 1% a day, and (3) no declaration of treatment failure because of intolerability or safety. Additional outcomes included time to sustained corticosteroid-sparing control of inflammation, change in best spectacle-corrected visual acuity, resolution of macular edema, adverse events, subgroup analysis by anatomic location, and medication adherence.ResultsForty-one patients were randomized to methotrexate and 39 to mycophenolate mofetil. A total of 67 patients (35 methotrexate, 32 mycophenolate mofetil) contributed to the primary outcome. Sixty-nine percent of patients achieved treatment success with methotrexate and 47% with mycophenolate mofetil (P = 0.09). Treatment failure from adverse events or tolerability was not different by treatment arm (P = 0.99). There were no differences between treatment groups in time to corticosteroid-sparing control of inflammation (P = 0.44), change in best spectacle-corrected visual acuity (P = 0.68), or resolution of macular edema (P = 0.31).ConclusionsThere was no statistically significant difference in corticosteroid-sparing control of inflammation between patients receiving methotrexate or mycophenolate mofetil. However, there was a 22% difference in treatment success favoring methotrexate.

AimTo evaluate the efficacy of a standardised combination therapy for clinically significant diabetic macular oedema using bevacizumab injections followed by navigated laser photocoagulation to stabilise retinal thickness.MethodsIn this pilot study we retrospectively reviewed charts and imaging of 23 eyes treated with the standardised combination regimen. Eyes initially received monthly bevacizumab injections, followed by navigated laser photocoagulation when central retinal thickness (CRT) was

PurposeFar-red/near-infrared phototherapy or photobiomodulation (PBM) has recently been reported to be an effective and non-invasive treatment method to inhibit lesions of diabetic retinopathy (DR) in animals. This study investigated the safety and efficacy of PBM in diabetic patients to treat non-center-involving diabetic macular oedema (NCDME).MethodsThis was a non-randomised, consecutive, case series, where 4 patients with type 2 diabetes with NCDME were treated for 160 s per day with PBM for 2-9 months. Demographic data including age, sex, HbA1c%, electronic ETDRS visual acuity, and retinal and macular thickness were measured using spectral domain ocular coherence tomography (SD-OCT) before and after treatment.ResultsFour eyes of 4 patients were treated, with fellow eyes serving as untreated controls. Daily PBM treatment for only 80 s per treatment twice daily caused a significant reduction in focal retinal thickening in all 4 treated eyes. No adverse effects attributable to therapy were noted by the patients or study investigators during the study period.ConclusionsPBM potentially offers a non-invasive and cost-effective therapeutic option for patients with NCDME. Further studies of this therapeutic option in DR are warranted.

PurposeTo compare laser photocoagulation plans for diabetic macular edema (DME) using fluorescein angiography (FA) versus optical coherence tomography (OCT) thickness map superimposed on the retina.MethodsFourteen eyes with DME undergoing navigated laser photocoagulation with navigated photocoagulator had FA taken using the same instrument. Optical coherence tomography central retinal thickness map was imported to the photocoagulator and with same magnification aligned onto the retina. Three retina specialists placed laser spot marks separately on FA and OCT image in a masked fashion. The spots placed by each physician were compared between FA and OCT and among physicians. The area of dye leakage on FA and increased central retinal thickness on OCT of the same eye were also compared.ResultsThe average number of spots using FA and OCT template was 36.64 and 40.61, respectively (P = 0.0201). The average area of dye leakage was 7.45 mm, whereas the average area of increased central retinal thickness on OCT of the same eye was 10.92 mm (P = 0.013).ConclusionThere is variability in the treatment planning for macular photocoagulation with a tendency to place more spots when guided by OCT than by FA. Integration of OCT map aligned to the retina may have an impact on treatment plan once such information is available.

PurposeTo evaluate the safety of oral fluorescein angiography (FA) and to compare its efficacy in detection of macular edema (ME) with spectral-domain optical coherence tomography (SD-OCT).MethodsResults of imaging studies for 1,928 eyes of 1,019 patients who had simultaneously undergone both oral FA and SD-OCT by a confocal laser ophthalmoscope were reviewed. Sensitivity in detecting ME, discrepancy rate, and "kappa" agreement were determined for both the techniques and with eyes stratified by disease diagnosis.ResultsNo allergic reactions occurred after oral FA. Mild gastric discomfort was noted in

ObjectiveTo evaluate agreement between fluorescein angiography (FA) and optical coherence tomography (OCT) results for diagnosis of macular edema in patients with uveitis.DesignMulticenter cross-sectional study.ParticipantsFour hundred seventy-nine eyes with uveitis from 255 patients.MethodsThe macular status of dilated eyes with intermediate uveitis, posterior uveitis, or panuveitis was assessed via Stratus-3 OCT and FA. To evaluate agreement between the diagnostic approaches, κ statistics were used.Main outcome measuresMacular thickening (MT; center point thickness, ≥ 240 μm per reading center grading of OCT images) and macular leakage (ML; central subfield fluorescein leakage, ≥ 0.44 disc areas per reading center grading of FA images), and agreement between these outcomes in diagnosing macular edema.ResultsOptical coherence tomography (90.4%) more frequently returned usable information regarding macular edema than FA (77%) or biomicroscopy (76%). Agreement in diagnosis of MT and ML (κ = 0.44) was moderate. Macular leakage was present in 40% of cases free of MT, whereas MT was present in 34% of cases without ML. Biomicroscopic evaluation for macular edema failed to detect 40% and 45% of cases of MT and ML, respectively, and diagnosed 17% and 17% of cases with macular edema that did not have MT or ML, respectively; these results may underestimate biomicroscopic errors (ophthalmologists were not explicitly masked to OCT and FA results). Among eyes free of ML, phakic eyes without cataract rarely (4%) had MT. No factors were found that effectively ruled out ML when MT was absent.ConclusionsOptical coherence tomography and FA offered only moderate agreement regarding macular edema status in uveitis cases, probably because what they measure (MT and ML) are related but nonidentical macular pathologic characteristics. Given its lower cost, greater safety, and greater likelihood of obtaining usable information, OCT may be the best initial test for evaluation of suspected macular edema. However, given that ML cannot be ruled out if MT is absent and vice versa, obtaining the second test after negative results on the first seems justified when detection of ML or MT would alter management. Given that biomicroscopic evaluation for macular edema erred frequently, ancillary testing for macular edema seems indicated when knowledge of ML or MT status would affect management.Financial disclosure(s)Proprietary or commercial disclosure may be found after the references.

BackgroundMicrocystic macular oedema (MMO) of the retinal inner nuclear layer (INL) has been identified in patients with multiple sclerosis (MS) by use of optical coherence tomography (OCT). We aimed to determine whether MMO of the INL, and increased thickness of the INL are associated with disease activity or disability progression.MethodsThis retrospective study was done at the Johns Hopkins Hospital (Baltimore, MD, USA), between September, 2008, and March, 2012. Patients with MS and healthy controls underwent serial OCT scans and clinical assessments including visual function. OCT scanning, including automated intraretinal layer segmentation, yielded thicknesses of the retinal nerve fibre layer, the ganglion cell layer plus inner plexiform layer, the INL plus outer plexiform layer (the combined thickness of these layers was used as a surrogate measure of INL thickness), and the outer nuclear layer. Patients with MS also underwent annual brain MRI scans. Disability scores were compared with the Wilcoxon rank-sum test. Mixed-effects linear regression was used to compare OCT measures and letter-acuity scores. Logistic regression was used to examine the relations of baseline OCT thicknesses with clinical and radiological parameters.Findings164 patients with MS and 60 healthy controls were assessed. Mean follow-up was 25·8 months (SD 9·1) for patients with MS and 22·4 months (11·4) for healthy controls. Ten (6%) patients with MS had MMO during at least one study visit; MMO was visible at baseline in four of these patients. Healthy controls did not have MMO. Patients with MS and MMO had higher baseline MS severity scores (median 5·93 [range 2·44-8·91]) than those who did not have MMO at any time during the study (151 patients; 3·81 [0·13-9·47]; p=0·032), although expanded disability status scale (EDSS) scores were not significantly different (5·2 [1·0-6·5] for patients with MS and MMO vs 2·5 [0·0-8·0] for those without MMO; p=0·097). The eyes of patients with MS and MMO (12 eyes) versus those without MMO (302 eyes) had lower letter-acuity scores (100% contrast, p=0·017; 2·5% contrast, p=0·031; 1·25% contrast, p=0·014), and increased INL thicknesses (p=0·003) at baseline. Increased baseline INL thickness in patients with MS was associated with the development of contrast-enhancing lesions (p=0·007), new T2 lesions (p=0·015), EDSS progression (p=0·034), and relapses in patients with relapsing-remitting MS (p=0·008) during the study. MMO was not associated with disease activity during follow-up.InterpretationIncreased INL thickness on OCT is associated with disease activity in MS. If this finding is confirmed, INL thickness could be a useful predictor of disease progression in patients with MS.FundingNational Multiple Sclerosis Society, National Eye Institute, Braxton Debbie Angela Dillon and Skip Donor Advisor Fund.