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

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

Dexamethasone Implants in Diabetic Macular Edema Patients with High Visual Acuity.

PURPOSE: To evaluate the effects of intravitreal dexamethasone (DEX) implants in patients affected by diabetic macular edema (DME) with high best-corrected visual acuity (BCVA) and contraindications to therapy with anti-vascular endothelial growth factor over a 12-month follow-up. METHODS: In this interventional nonrandomized clinical study, 14 consecutive patients (14 eyes) affected by DME with a BCVA of 0.3 LogMAR or better were prospectively enrolled. All patients were treated with a sustained-release 700-µg DEX implant at baseline, revaluated every 6 weeks, and retreated on a pro re nata basis. Primary outcomes included changes in BCVA and central macular thickness (CMT). Secondary outcomes included number of implants, average period between injections, and incidence of side effects. RESULTS: At the 12-month examination, a significant improvement in mean BCVA was noted compared to baseline (from 0.25 ± 0.05 to 0.10 ± 0.07 LogMAR; p < 0.001); CMT decreased from 484 ± 127 to 311 ± 51 µm (p < 0.001). No differences in BCVA and CMT improvements were found between treatment- naïve patients and previously treated patients (p = 0.768 and 0.119, respectively). The mean number of implants was 1.71 ± 0.61 (range, 1-3). The mean period between the first and the second implant was 6.1 ± 1.6 months. CONCLUSIONS: The DEX implant on a pro re nata basis can be considered a beneficial approach for DME patients with high BCVA over a 12-month follow-up; functional and anatomical outcome of the patients significantly improved with few injections and a good safety profile.

Repeated intravitreal dexamethasone implant (Ozurdex) for diabetic macular edema.

PURPOSE: To evaluate the effects of repeated intravitreal dexamethasone implant. METHODS: We reviewed the charts of 12 patients with diabetic macular edema, who received at least 2 intravitreal Ozurdex (0.7 mg) on an "as needed" basis. Main outcome measures included changes in best-corrected visual acuity, central macular thickness, retreatment interval, and incidence of side effects. RESULTS: A total of 15 eyes of 12 patients (6 men, 6 women; mean age 62 ± 12 years) were included. Retreatment was judged necessary after mean of 7.8 ± 4.1 months from the first Ozurdex (median, 6 months) (15 of 15 eyes), mean of 4.8 ± 0.9 months from the second Ozurdex (median, 5 months) (7 of 15 eyes), mean of 5.3 ± 1.5 months from the third Ozurdex (median, 5 months) (3 of 15 eyes), and mean of 5.6 ± 2 months from the fourth Ozurdex (median, 5 months) (3 of 15 eyes). Mean baseline best-corrected visual acuity was 0.67 ± 0.33 logMAR in the overall diabetic macular edema population; it significantly improved to 0.53 ± 0.31 logMAR after mean of 40.9 ± 18.2 days from the first Ozurdex (peaking efficacy) (P < 0.001), to 0.53 ± 0.29 logMAR after mean of 34.4 ± 9.0 days from the second Ozurdex (peaking efficacy) (P < 0.003), and stabilized to 0.62 ± 0.26 logMAR after mean of 29.8 ± 12.1 days from the third Ozurdex (peaking efficacy) (P = 0.05), to 0.5 ± 0.26 logMAR after mean of 36.3 ± 3.2 days from the fourth Ozurdex (peaking efficacy) (P = 0.2), and to 0.50 ± 0.26 logMAR after mean of 37.0 ± 2.6 days from the fifth Ozurdex (peaking efficacy) (P = 0.2). Mean baseline central macular thickness significantly decreased from 546 ± 139 µm to 292 ± 43 µm at 39.4 ± 17.9 days from the first Ozurdex (peaking efficacy) (P < 0.001), to 297 ± 47 µm at 33 ± 9.4 days from the second Ozurdex (peaking efficacy) (P < 0.001), to 293 ± 22 µm at 29.8 ± 12.1 days from the third Ozurdex (peaking efficacy) (P = 0.01), and stabilized to 309 ± 35 µm at 36.3 ± 3.2 days from the fourth Ozurdex (peaking efficacy) (P = 0.1), and to 295 ± 7 µm at 37.0 ± 2.6 days from the fifth Ozurdex (peaking efficacy) (P = 0.1). No serious adverse events were observed; three eyes developed a transient intraocular pressure increase, and cataract was extracted in one eye. CONCLUSION: Repeated intravitreal Ozurdex on an "as needed" basis with a variable retreatment interval may produce long-term clinically meaningful benefits in the treatment of diabetic macular edema, without other significant side effects than expected after intraocular corticosteroid treatment.

Optical coherence tomographic hyperreflective foci in early stages of diabetic retinopathy.

PURPOSE: To analyze the presence of hyperreflective foci in Type 1 and Type 2 diabetic patients, separately, without clinically significant diabetic macular edema and visual impairment. METHODS: Noninvasive, observational prospective study. Seventeen and 19 consecutive Type 1 and Type 2 diabetic patients (33 and 38 eyes), respectively, were recruited. All patients had no clinically significant diabetic macular edema or visual impairment. Two age- and sex-matched control groups were also included. Patients underwent an ophthalmologic examination including spectral domain optical coherence tomography. Hyperreflective foci were counted considering horizontal B-scan passing through the fovea. RESULTS: On spectral domain optical coherence tomography, patients affected by Type 1 and Type 2 diabetes had a mean of 7.5 ± 4.6 and 9.9 ± 4.5 hyperreflective foci, respectively. Subjects of control groups had a mean of 0.9 ± 0.8 and 1.7 ± 1.5 hyperreflective foci, respectively. Hyperreflective foci amount was statistically different between Type 1 and Type 2 diabetic groups (P = 0.032) and significantly higher in diabetic patients than in controls (P < 0.001). Hyperreflective foci amount was significantly higher in diabetic patients with a poor quality glycometabolic control (P < 0.001 and P = 0.016) or affected by hypertension (P = 0.008). CONCLUSION: We reported the presence of hyperreflective foci in diabetic patients without diabetic macular edema and visual impairment. This spectral domain optical coherence tomography finding might be a useful marker for the diagnosis and the follow-up in the early stage of diabetic retinopathy.

DYNAMIC AND STATIC RETINAL VESSEL ANALYSES IN PATIENTS WITH MACULAR EDEMA SECONDARY TO RETINAL VEIN OCCLUSION.

PURPOSE: To investigate the vasomotor responses and diameter of retinal vessels in patients with macular edema secondary to retinal vein occlusion (RVO). METHODS: A total of 18 eyes of 18 RVO patients were consecutively included and compared with age- and sex-matched controls. Participants underwent an examination with optical coherence tomography and dynamic and static retinal vessel analyses using the Dynamic Vessel Analyzer. RESULTS: Dynamic vessel analysis in RVO showed mean maximum venous and arterial dilation of 2.22 ± 1.23% and 1.87 ± 1.41%, respectively, as compared with 5.05 ± 2.75% (P = 0.001) and 3.95 ± 1.44% (P = 0.0004), respectively, in controls. Static retinal vessel analysis in RVO revealed a mean arteriovenous ratio (AVR) of 0.74 ± 0.09 versus 0.90 ± 0.04 (P < 0.0001) in controls. Mean AVRs of occluded and nonoccluded quadrants in RVO were 0.71 ± 0.13 and 0.85 ± 0.19, respectively; in the corresponding quadrants of controls, mean AVRs were 0.90 ± 0.19 (P < 0.0001) and 0.86 ± 0.17 (P = 0.89), respectively. In branch RVO patients, mean AVRs of occluded versus nonoccluded quadrants were 0.70 ± 0.06 and 0.90 ± 0.22 (P = 0.002), respectively. CONCLUSION: In patients with macular edema secondary to RVO, dynamic vessel analysis showed an impairment of both venous and arterial motility and/or reactivity and static vessel analysis showed a reduced AVR indicating a general enlargement of the retinal venous network. Moreover, in branch RVO patients, static analysis demonstrated that retinal vessels could actually be uninvolved by the occlusive process in areas spared by disease.

Prospective evaluation of morphological and functional changes after repeated intravitreal dexamethasone implant (Ozurdex®) for retinal vein occlusion.

AIMS: To evaluate changes in macular morphology and function after repeated intravitreal dexamethasone implant (Ozurdex®) for macular edema (ME) due to retinal vein occlusion (RVO). METHODS: Consecutive treatment-naïve patients with ME secondary to RVO were treated with Ozurdex and followed up to 12 months to evaluate functional and morphological outcomes by means of best-corrected visual acuity (BCVA) and microperimetry and by enhanced depth imaging optical coherence tomography, respectively. RESULTS: Thirty-five eyes of 35 patients were included for the analysis (26 central RVO, 9 branch RVO). During the 12-month study period, 8 of the 35 eyes (23%) underwent 1 intravitreal dexamethasone implant, 13 of the 35 eyes (37%) underwent 2, and 14 of the 35 eyes (40%) underwent 3 intravitreal dexamethasone implants. At 1 month from the 1st intravitreal dexamethasone implant, the mean BCVA, retinal sensitivity and central macular thickness (CMT) significantly improved compared to the baseline values. At 3 months, the mean BCVA improvement was no more significant, while retinal sensitivity further improved and CMT slightly worsened, remaining, however, significantly better than at baseline. At 12 months, those eyes that had undergone 2 retreatments showed a significant improvement of the mean BCVA, mean retinal sensitivity and CMT compared to the baseline values [0.61 ± 0.29 logarithm of the minimum angle of resolution (LogMAR) vs. 0.82 ± 0.33 LogMAR, p = 0.011; 12.94 ± 4.73 dB vs. 10.75 ± 3.27 dB, p = 0.043, and 321 ± 91 µm vs. 735 ± 169 µm, p = 0.001, respectively]. In those eyes that had undergone only 1 retreatment, a significant improvement was recorded only for the CMT (500 ± 224 µm vs. 695 ± 302 µm, p = 0.044). The mean retreatment interval between the 1st and the 2nd injection was 4.5 ± 1.1 months (range 3-7 months), and between the 2nd and the 3rd injection it was 4.1 ± 1 months (range 3-6 months). CONCLUSIONS: In eyes with ME secondary to RVO, Ozurdex produces functional benefits as early as 1 month after treatment/retreatment. Current optical coherence tomography and microperimetry findings confirm the concept that, in most cases, the optimum retreatment interval should be <6 months from the 1st injection.

Impact of intravitreal dexamethasone implant (Ozurdex) on macular morphology and function.

PURPOSE: To investigate the impact of intravitreal dexamethasone implant (Ozurdex) on macular morphology and function in eyes with macular edema secondary to central retinal vein occlusion. METHODS: Twelve treatment-naive patients with decreased visual acuity because of central retinal vein occlusion-related macular edema were enrolled in this prospective uncontrolled study. Patients were treated with intravitreal Ozurdex and followed up at 1 month and 3 months for the evaluation of morphologic and functional outcomes, by means of best-corrected visual acuity, microperimetry, multifocal electroretinography, and customized high-resolution enhanced depth imaging spectral-domain optical coherence tomography scans. RESULTS: Twelve eyes of 12 patients (10 men, 2 women; mean age 56.2 ± 13.0 years) were included for analysis. At 1 month, mean best-corrected visual acuity, retinal sensitivity (microperimetry), multifocal electroretinography parameters, central macular thickness, and specific neurosensorial retinal measurements improved significantly. We found a significant negative correlation between retinal sensitivity and central macular thickness at 1 month and 3 months (r = -0.831, P = 0.001; r = -0.881, P = 0.001; respectively). Moreover, retinal sensitivity was negatively related to both outer and inner retinal thickness in all four intervals from the fovea. From baseline to Month 1, change in outer retinal thickness was positively related to multifocal electroretinography N1R1 amplitude change (r = 0.698, P = 0.012), whereas change in central macular thickness was negatively related to multifocal electroretinography P1R1 amplitude change (r = -0.701, P = 0.011). At 3 months, improvement of mean retinal sensitivity and central macular thickness slightly decreased. CONCLUSION: In eyes with macular edema secondary to central retinal vein occlusion, intravitreal dexamethasone provides functional benefits that correlate well with ultrastructural macular changes.

Macular dysfunction is common in both type 1 and type 2 diabetic patients without macular edema.

PURPOSE: To study retinal function in asymptomatic Type 1 and Type 2 diabetic patients with nonproliferative diabetic retinopathy (NPDR) and no clinical signs of diabetic macular edema. METHODS: Thirty-six consecutive Type 1 and Type 2 diabetic patients with nonproliferative diabetic retinopathy and no diabetic macular edema and 28 healthy controls underwent a complete ophthalmologic examination, including spectral domain optical coherence tomography and microperimetry. RESULTS: Seventy-one eyes (17 patients with Type 1 and 19 with Type 2 diabetes) were tested, and data from 36 (17 Type 1 and 19 Type 2) eyes were analyzed. Mean best-corrected visual acuity was 0.00 ± 0.01 logMAR and 0.00 ± 0.02 logMAR for Type 1 and Type 2 diabetic patients, respectively (P = 0.075). Mean central foveal thickness was 234.5 ± 13.7 µm and 256.3 ± 12.7 µm for Type 1 and Type 2 diabetic patients, respectively (P = 0.04); the central foveal thickness was statistically different compared with the control groups (P = 0.04 and P = 0.01, respectively). Mean retinal sensitivity was 18.9 ± 0.5 dB and 17.7 ± 0.4 dB for Type 1 and Type 2 diabetic patients, respectively; it was statistically different compared with control groups (P < 0.0001 and P < 0.0001, respectively). CONCLUSION: We demonstrated a significantly reduced sensitivity in both nonproliferative diabetic retinopathy groups without diabetic macular edema compared with healthy controls; this reduction was greater in Type 2 diabetic patients. Central foveal thickness was increased in all diabetic patients compared with healthy controls, despite the absence of diabetic macular edema.

Changes in macular function after ozurdex for retinal vein occlusion.

PURPOSE: To investigate changes in macular function after intravitreal dexamethasone implant (Ozurdex) for macular edema (ME) secondary to retinal vein occlusion (RVO). METHODS: Nineteen treatment-naive patients with RVO-related ME were treated with intravitreal Ozurdex and followed up to 6 months to evaluate functional outcomes, by means of best-corrected visual acuity, microperimetry, and multifocal electroretinography, and their correlations with morphological parameters by enhanced depth imaging optical coherence tomography. RESULTS: Nineteen eyes of 19 patients were included for analysis. At 1 month, mean best-corrected visual acuity, retinal sensitivity, and central macular thickness (CMT) improved from 0.50 ± 0.34 LogMAR, 10.51 ± 4.31 dB, and 762 ± 259 µm (baseline) to 0.38 ± 0.34 LogMAR (p = 0.043), 12.28 ± 5.06 dB (p = 0.025), and 385 ± 191 µm (p = 0.001), respectively. At 3 months, improvement of mean retinal sensitivity and CMT was still significant (11.62 ± 5.05 dB [p = 0.047] and 518 ± 251 µm [p = 0.006]). Multifocal electroretinography measurements also showed (nonsignificant) improvement. No significant changes in choroidal thickness were recorded. Improvements recorded during the first 3 months were no longer significant from month 4. At each time point, we found a negative significant correlation between CMT and retinal sensitivity. Interestingly, 7 eyes did not undergo retreatment of less than 6 months; these eyes showed a significantly better baseline retinal sensitivity than eyes requiring retreatment of less than 6 months (12.27 ± 3.52 dB vs. 9.48 ± 4.53 dB [p = 0.038]). CONCLUSIONS: In eyes with ME secondary to RVO, intravitreal dexamethasone implant provides functional benefits as soon as 1 month after treatment. In most cases, the optimum retreatment interval is less than 6 months from first intravitreal Ozurdex. Microperimetry is a very useful tool to characterize macular function. Baseline macular sensitivity may predict the need for early (<6 months) retreatment.

Update of intravitreal steroids for the treatment of diabetic macular edema.

Diabetic macular edema is considered the most important factor related to visual impairment in patients with diabetic retinopathy. Together with the use of grid and focal laser photocoagulation, today the intravitreal administration of pharmacotherapies represents the standard of care for the treatment of this complication: anti-vascular endothelium growth factor agents and steroids are the drugs currently used for this aim. Differently from laser therapy, which prevents visual deterioration, the intravitreal approach allows the promotion of visual recovery. However, the intravitreal injections require to be repeated with high frequency, and this carries the risk of drug- and procedure-related adverse effects.

From diagnosis to prognosis: A paradigm shift for multimodal imaging in assessing diabetic macular edema.

Diabetic macular edema (DME) is one of the leading causes of visual impairment in patients with diabetes. Multimodal imaging (MMI) has allowed a shift from DME diagnosis to prognosis. Although there are no accepted guidelines, MMI may also lead to treatment customization. Several study groups have tried to identify structural biomarkers that can predict treatment response and long-term visual prognosis. The purpose of this editorial is to review currently proposed optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A) biomarkers.

Rate and Predictors of Misclassification of Active Diabetic Macular Edema as Detected by an Automated Retinal Image Analysis System.

INTRODUCTION: The aim of this work is to estimate the sensitivity, specificity, and misclassification rate of an automated retinal image analysis system (ARIAS) in diagnosing active diabetic macular edema (DME) and to identify factors associated with true and false positives. METHODS: We conducted a cross-sectional study of prospectively enrolled patients with diabetes mellitus (DM) referred to a tertiary medical retina center for screening or management of DME. All patients underwent two-field fundus photography (macula- and disc-centered) with a true-color confocal camera; images were processed by EyeArt V.2.1.0 (Woodland Hills, CA, USA). Active DME was defined as the presence of intraretinal or subretinal fluid on spectral-domain optical coherence tomography (SD-OCT). Sensitivity and specificity and their 95% confidence intervals (CIs) were calculated. Variables associated with true (i.e., DME labeled as present by ARIAS + fluid on SD-OCT) and false positives (i.e., DME labeled as present by ARIAS + no fluid on SD-OCT) of active DME were explored. RESULTS: A total of 298 eyes were included; 92 eyes (31%) had active DME. ARIAS sensitivity and specificity were 82.61% (95% CI 72.37-89.60) and 84.47% (95% CI 78.34-89.10). The misclassification rate was 16%. Factors associated with true positives included younger age (p = 0.01), shorter DM duration (p = 0.006), presence of hard exudates (p = 0.005), and microaneurysms (p = 0.002). Factors associated with false positives included longer DM duration (p = 0.01), worse diabetic retinopathy severity (p = 0.008), history of inactivated DME (p < 0.001), and presence of hard exudates (p < 0.001), microaneurysms (p < 0.001), or epiretinal membrane (p = 0.06). CONCLUSIONS: The sensitivity of ARIAS was diminished in older patients and those without DME-related fundus lesions, while the specificity was reduced in cases with a history of inactivated DME. ARIAS performed well in screening for naïve DME but is not effective in surveillance inactivated DME.

Assessing Diabetic Retinopathy Staging With AI: A Comparative Analysis Between Pseudocolor and LED Imaging.

Purpose: To compare the diagnostic performance of artificial intelligence (AI)-based diabetic retinopathy (DR) staging system across pseudocolor, simulated white light (SWL), and light-emitting diode (LED) camera imaging modalities. Methods: A cross-sectional investigation involved patients with diabetes undergoing imaging with an iCare DRSplus confocal LED camera and an Optos confocal, ultra-widefield pseudocolor camera, with and without SWL. Macula-centered and optic nerve-centered 45 × 45-degree photographs were processed using EyeArt v2.1. Human graders established the ground truth (GT) for DR severity on dilated fundus exams. Sensitivity and weighted Cohen's weighted kappa (wκ) were calculated. An ordinal generalized linear mixed model identified factors influencing accurate DR staging. Results: The study included 362 eyes from 189 patients. The LED camera excelled in identifying sight-threatening DR stages (sensitivity = 0.83, specificity = 0.95 for proliferative DR) and had the highest agreement with the GT (wκ = 0.71). The addition of SWL to pseudocolor imaging resulted in decreased performance (sensitivity = 0.33, specificity = 0.98 for proliferative DR; wκ = 0.55). Peripheral lesions reduced the likelihood of being staged in the same or higher DR category by 80% (P < 0.001). Conclusions: Pseudocolor and LED cameras, although proficient, demonstrated non-interchangeable performance, with the LED camera exhibiting superior accuracy in identifying advanced DR stages. These findings underscore the importance of implementing AI systems trained for ultra-widefield imaging, considering the impact of peripheral lesions on correct DR staging. Translational Relevance: This study underscores the need for artificial intelligence-based systems specifically trained for ultra-widefield imaging in diabetic retinopathy assessment.

Management of treatment-naïve diabetic macular edema patients: Review of real-world clinical data.

The high prevalence of Diabetic macular edema (DME) is a real global health problem. Its complex pathophysiology involves different pathways. Over the last decade, the introduction of intravitreal treatments has dramatically changed the management and prognosis of DME. Among the different treatment options, inhibitors of vascular endothelial growth factor (anti-VEGF) and intravitreal steroids implants represent the first-line therapy of DME. We conducted a review of electronic databases to compile the available evidence about the clinical management of DME in a clinical setting, with a special focus on treatment-naïve patients. Anti-VEGF therapies represent a valuable option for treating DME patients. However, many patients do not respond properly to this treatment and, due to its administration regimen, many patients receive suboptimal treatment in real life. Current evidence demonstrated that in patients with DME, DEX-i improved significantly both anatomic and visual outcomes. Besides eyes with insufficient anti-VEGF respond or recalcitrant DME cases, DEX-i can be effectively and safely used in treatment-naïve DME patients as first line therapy. DEX-i may be considered first line therapy in different clinical scenarios, such as DME eyes with a greater inflammatory component, patients with cardiovascular events, vitrectomized eyes, or those requiring cataract surgery. In conclusion, there are still many points for improvement pending in the clinical management of the patient with DME. Since DME treatment must follow a patient-tailored approach, selecting the best therapeutic approach for each patient requires a good understanding of the pathophysiology of DME.

Rate and associations of inner retinal thinning in eyes with retinal vein occlusion and regressed macular oedema.

PURPOSE: To investigate the associations between visual acuity (VA) and structural optical coherence tomography (OCT) features in retinal vein occlusion (RVO) eyes after cystoid macular oedema (CMO) regression and to assess whether inner retinal thinning is progressive. METHODS: Retrospective observational study of RVO eyes with regressed CMO for at least 6 months. OCT scans at CMO regression were analysed, and features were correlated with VA at that visit. The inner retinal thickness was longitudinally compared between RVO and unaffected fellow eyes (controls) with linear mixed models. The rate of inner retinal thinning was obtained as the interaction term between disease status and time. Associations between inner retinal thinning and clinical characteristics were explored. RESULTS: Thirty-six RVO eyes were followed for 34.2 ± 21.1 months after CMO regression. The presence of ellipsoid zone disruption (regression estimate[standard error(SE)] = 0.16[0.04] LogMAR vs. intact, p < 0.001) and lower inner retinal thickness (regression estimate[SE] = -0.25[0.12] LogMAR for 100-µm increase, p = 0.01) were associated with worse VA. The inner retinal thickness decreased faster in RVO than controls (rate of retinal thinning -0.27 ± 0.09 µm/month vs. -0.08 ± 0.11 µm/month, p = 0.01). Macular ischaemia was associated with a faster rate of retinal thinning (interaction term macular ischaemia*follow-up time, p = 0.04). CONCLUSION: Inner retinal and photoreceptors' layers integrity are associated with better visual acuity once CMO resolves. RVO eyes undergo progressive inner retinal thinning after CMO regression, faster in eyes with macular ischaemia.

Real-world experience with fluocinolone acetonide intravitreal implant in patients with diabetic macular edema.

OBJECTIVES: to evaluate long-term effectiveness and safety of fluocinolone acetonide (FAc) implant used as second-line treatment in patients with persistent diabetic macular edema (DME). METHODS: retrospective data chart review of 241 pseudophakic eyes of 178 patients treated with FAc from July 2017 to December 2021 in 10 medical retinal units in Italy. The primary endpoint was the change of best-corrected visual acuity (BCVA) and central macular thickness (CMT) at 2 years. A Student's paired t-test was used. Additional therapies for DME and intraocular pressure (IOP)-related events were also evaluated. RESULTS: efficacy of FAc was assessed in a subset of 111 eyes with at least 24 months of follow-up. Mean BCVA increased at 2 years by 5.1 ETDRS letters (95%CI = 2.6-7.5; p < 0.001) while mean CMT decreased by 189 µm (95% CI 151-227; p < 0.001). Thirty-eight of these eyes (34.2%) needed additional intravitreal treatments, mainly anti-VEGF. Safety was evaluated on the entire cohort of 241 eyes treated with FAc. Overall, 66 eyes (27.4%) required emergent IOP-lowering medications (typically within the first-year post FAc) while 14 eyes (5.8%) underwent trabeculectomy, mostly during the second year of follow-up. CONCLUSION: FAc implant provides a substantial long-term functional and anatomical benefit when used as second-line treatment in eyes with DME. IOP rise can be adequately managed with topical agents although some eyes may require IOP-lowering surgery.

Repeated intravitreal dexamethasone implant (Ozurdex®) for retinal vein occlusion.

PURPOSE: To evaluate the effects of repeated intravitreal dexamethasone implant (IDI) (Ozurdex®) in eyes with macular edema (ME) due to retinal vein occlusion (RVO). METHODS: We reviewed the charts of patients with RVO-related ME, who received repeated Ozurdex IDI (0.7 mg) on an 'as-needed' basis. Main outcome measures included changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), retreatment interval, and incidence of side effects. RESULTS: A total of 33 eyes were included for analysis. Retreatment with Ozurdex was judged necessary after 4.7 ± 1.1 months from the first IDI (1st IDI) and 5.1 ± 1.5 months from the second IDI (2nd IDI). Baseline BCVA was 0.65 ± 0.43 logMAR; it significantly improved to 0.50 ± 0.42 logMAR after 1.4 ± 0.7 months from the 1st IDI (peaking efficacy) (p < 0.001) and to 0.48 ± 0.44 logMAR after 1.8 ± 0.8 months from the 2nd IDI (peaking efficacy) (p < 0.001). CMT decreased from 636 ± 217 µm (baseline) to 300 ± 114 µm, 1.4 ± 0.7 months after the 1st IDI (p < 0.001), and to 298 ± 91 µm, 1.8 ± 0.8 months after the 2nd IDI (p < 0.001). A rebound effect was recorded in 7 eyes after the 1st IDI (mean 168 ± 158 µm) and in 4 eyes after the 2nd IDI (mean 215 ± 199 µm). All eyes with a rebound effect improved again after a 2nd intravitreal Ozurdex injection. No serious adverse events were observed; 12 eyes developed a transient IOP increase, and cataracts were extracted in 2 eyes. CONCLUSION: Repeated intravitreal Ozurdex on an 'as-needed' basis, with a retreatment interval <6 months, may produce long-term clinically meaningful benefits in the treatment of ME due to RVO, without other significant side effects than expected after intraocular corticosteroid treatment.

Imaging Biomarkers of Mesopic and Dark-Adapted Macular Functions in Eyes With Treatment-Naïve Mild Diabetic Retinopathy.

PURPOSE: To investigate the relationship between imaging biomarkers and mesopic and dark-adapted (ie, scotopic) functions in patients with treatment-naïve mild diabetic retinopathy (DR) and normal visual acuity. DESIGN: Prospective cross-sectional study. METHODS: In this study, 60 patients with treatment-naïve mild DR (Early Treatment of Diabetic Retinopathy Study levels 20-35) and 30 healthy control subjects underwent microperimetry, structural optical coherence tomography (OCT), and OCT angiography (OCTA). RESULTS: The foveal mesopic (22.4 ± 4.5 dB and 25.8 ± 2.0 dB, P = .005), parafoveal mesopic (23.2 ± 3.8 and 25.8 ± 1.9, P < .0001), and parafoveal dark-adapted (21.1 ± 2.8 dB and 23.2 ± 1.9 dB, P = .003) sensitivities were reduced in DR eyes. For foveal mesopic sensitivity, the regression analysis showed a significant topographic association with choriocapillaris flow deficits percentage (CC FD%; ß = -0.234, P = .046) and ellipsoid zone (EZ) normalized reflectivity (ß = 0.282, P = .048). Parafoveal mesopic sensitivity was significantly topographically associated with inner retinal thickness (ß = 0.253, P = .035), deep capillary plexus (DCP) vessel length density (VLD; ß = 0.542, P = .016), CC FD% (ß = -0.312, P = .032), and EZ normalized reflectivity (ß = 0.328, P = .031). Similarly, parafoveal dark-adapted sensitivity was topographically associated with inner retinal thickness (ß = 0.453, P = .021), DCP VLD (ß = 0.370, P = .030), CC FD% (ß = -0.282, P = .048), and EZ normalized reflectivity (ß = 0.295, P = .042). CONCLUSIONS: In treatment-naïve mild DR eyes, both rod and cone functions are affected and they are associated with both DCP and CC flow impairment, which suggests that a macular hypoperfusion at these levels might implicate a reduction in photoreceptor function. Normalized EZ reflectivity may be a valuable structural biomarker for assessing photoreceptor function in DR. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Factors associated with the response to fluocinolone acetonide 0.19 mg in diabetic macular oedema evaluated as the area-under-the-curve.

OBJECTIVES: The area-under-the-curve (AUC) measures the average drug effect over time. We investigated the impact of baseline clinical and optical coherence tomography (OCT) factors on the response to fluocinolone acetonide (FAc) 0.19 mg implant in patients with diabetic macular oedema (DMO) as the AUC over 36 months. METHODS: Retrospective study of DMO eyes undergoing FAc with follow-up from 12 to 36 months. The AUC of the best-corrected visual acuity (BCVA) and the central macular thickness (CMT) were calculated with the trapezoidal rule. Demographic and clinical data at the time of FAc administration were collected, and associations with BCVA and CMT changes were investigated with linear mixed models. RESULTS: Eighty-nine eyes of 63 patients were enroled; median follow-up was 26 months. Mean±standard deviation (SD) AUCBCVA and AUCCMT after FAc injection were 0.24 ± 0.17 LogMAR/month and 179.6 ± 54.3 µm/month, respectively. Worse baseline BCVA (ß = 0.30 LogMAR/month, p < 0.001), higher AUCCMT after FAc administration (ß = 0.08 LogMAR/month, p < 0.001), diagnosis of type 1 diabetes (ß = -0.04 LogMAR/month, p = 0.04), and absent ELM/EZ layers (ß = 0.06 LogMAR/month, p = 0.01) were associated with worse vision over time (higher AUCBCVA). Eyes with higher CMT at baseline (ß = 9.61 µm/month, p < 0.001) and those with tractional DMO (ß = 24.7 µm/month, p = 0.01) had worse anatomic outcomes (higher AUCCMT). The need for additional treatments after FAc was also associated with higher AUCCMT (ß = 33.9 µm/month, p = 0.001). CONCLUSION: Baseline better visual acuity, lower macular thickness, and photoreceptors' layers integrity are associated with better functional response to FAc in DMO. Eyes with severe DMO at the time of implant or tractional oedema have worse anatomic response. These findings might guide clinicians in a more informed decisional algorithm in treating DMO.

CLINICAL CHARACTERISTICS AND MULTIMODAL IMAGING FINDINGS IN UNILATERAL FROSTED BRANCH ANGIITIS: A CASE REPORT.

PURPOSE: Our aim is to report a comprehensive multimodal imaging case of unilateral frosted branch angiitis in a 40-years-old Caucasian female . METHODS: Case report involving clinical examination, ultra- wide field fundus photograph, ultra-wide field fluorescein angiography (UWFA), optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). RESULTS: A 40 years old patients presented with unilateral acute vision loss. On fundus examination, extensive retinal veins sheathing, macular edema and vascular congestion were observed while UWFA revealed an hyperfluorescent "hot" optic disc and blood retinal barrier disruption. OCTA displayed foveal avascular zone (FAZ) enlargement and excluded papillary neovascularization. Extensive laboratory work-up for infectious, autoimmune and inflammatory disorders were negative, thus, a diagnose of acute idiopathic unilateral frosted branch angiitis was made. Intravitreal injection of dexamethasone implant was administered with a good clinical response. CONCLUSIONS: Multimodal imaging is crucial to correctly diagnose and treat FBA. Up to our knowledge, the use of OCTA as a complementary tool to the diagnostic process in FBA has been described in literature just once as a photo essay of cytomegalovirus-related FBA and it might be of great value for better characterizing clinical features of this disorder and for following disease activity in a non-invasive fashion.