GRAding of functional and anatomical response to DExamethasone implant in patients with Diabetic Macular Edema: GRADE-DME Study.

To analyze functional and anatomical response patterns to dexamethasone (DEX) implant in diabetic macular edema (DME), to describe proportion of responders and non-responders, and to propose a new DME grading system. Retrospective, multicenter, observational cohort study. Naïve and non-naïve DME patients were treated with DEX, with visual acuity (VA) ≥ 0.2 logMAR and central subfield thickness (CST) of ≥ 300 µm. Functional and anatomical responses were graded after 2 and 4 months, and categorized as early and stable improvement, early and progressive improvement, pendular response, delayed improvement, and persistent non-response. 417 eyes were included (175 treatment naïve eyes). Compared to non-naïve eyes, naïve eyes showed a very good functional response (VA gain ≥ 10 letters) more frequently after 2 and 4 months (56% and 57% [naïve] vs. 33% and 28% [non-naïve], p < 0.001). A VA gain < 5 letters (non-response) after 2 and 4 months was seen in 18% and 16% of naïve eyes, and in 49% and 53% of non-naïve eyes (p < 0.001). A lack of anatomical response was rare in both groups, but more frequently in non-naïve eyes (12% vs. 4%, p = 0.003). Functionally and anatomically, naïve eyes showed most frequently an early and stable improvement (functionally: 77/175 44%; anatomically: 123/175 eyes, 70%). Most non-naïve eyes experienced no significant improvement functionally (97/242 eyes, 40%), despite a mostly early and stable improvement anatomical response pattern (102/242 eyes, 42%). Functional but not anatomical response patterns were influenced by baseline VA. Naïve and non-naïve eyes show different functional and anatomical response patterns to DEX implant. Functional non-responders are rare in naïve eyes, whereas anatomical non-response is unusual in both groups.

DEXAMETHASONE IMPLANT FOR DIABETIC MACULAR EDEMA IN NAIVE COMPARED WITH REFRACTORY EYES: The International Retina Group Real-Life 24-Month Multicenter Study. The IRGREL-DEX Study.

PURPOSE: To investigate efficacy and safety of repeated dexamethasone (DEX) implants over 24 months, in diabetic macular edema (DME) eyes that were treatment naive compared with eyes refractory to anti-vascular endothelial growth factor treatment, in a real-life environment. METHODS: This multicenter international retrospective study assessed best-corrected visual acuity and central subfield thickness (CST) of naive and refractory eyes to anti-vascular endothelial growth factor injections treated with dexamethasone implants. Safety data (intraocular pressure rise and cataract surgery) were recorded. RESULTS: A total of 130 eyes from 125 patients were included. Baseline best-corrected visual acuity and CST were similar for naive (n = 71) and refractory eyes (n = 59). Both groups improved significantly in vision after 24 months (P < 0.001). However, naive eyes gained statistically significantly more vision than refractory eyes (+11.3 ± 10.0 vs. 7.3 ± 2.7 letters, P = 0.01) and were more likely to gain ≥10 letters (OR 3.31, 95% CI 1.19-9.24, P = 0.02). At 6, 12, and 24 months, CST was significantly decreased compared with baseline in both naive and refractory eyes; however, CST was higher in refractory eyes than in naive eyes (CST 279 ± 61 vs. 313 ± 125 µm, P = 0.10). CONCLUSION: Over a follow-up of 24 months, vision improved in diabetic macular edema eyes after treatment with dexamethasone implants, both in eyes that were treatment naive and eyes refractory to anti-vascular endothelial growth factor treatment; however, improvement was greater in naive eyes.

UNDERDIAGNOSED OPTIC DISK PIT MACULOPATHY: Spectral Domain Optical Coherence Tomography Features For Accurate Diagnosis.

PURPOSE: To report a cohort with optic disk pit maculopathy (ODPM) presenting with neurosensory macular detachment that were initially misdiagnosed and mistreated; and to describe structural features on spectral domain optical coherence tomography in misdiagnosed and all other consecutive cases of ODPM. METHODS: Multicenter international retrospective cohort study. PARTICIPANTS: 59 eyes from 59 patients with ODPM. MAIN OUTCOME MEASURES: 1) Proportion of patients with ODPM initially misdiagnosed, inaccurate diagnosis and treatment. 2) Morphologic features on spectral domain optical coherence tomography: other causes of subretinal and/or intraretinal fluid, inner/outer retinoschisis, communication with optic disk pit, and retinal pigment epithelium alterations. 3) Visual and anatomical outcomes 6 months after proper treatment. RESULTS: Fifteen patients (25.4%) with ODPM were correctly diagnosed initially and those were significantly younger than misdiagnosed cases (age 33.8 ± 15.2 vs. 58.7 ± 15.8 years, P < 0.0001). Forty of forty-four misdiagnosed eyes (90.9%) were treated for their presumed diagnosis before referral. Eyes with initial misdiagnosis had significantly more outer retinoschisis at baseline (88.4 vs. 40.0%, P = 0.0002) and more retinal pigment epithelium alterations (90.0 vs. 27.3%, P < 0.0001) 6 months after proper treatment. CONCLUSION: Optic disk pit maculopathy is an underdiagnosed entity and can mimic other causes for subretinal fluid. Awareness and identification of pertinent spectral domain optical coherence tomography features can help avoid inappropriate and delayed treatment.

Biomarkers and predictors for functional and anatomic outcomes for small gauge pars plana vitrectomy and peeling of the internal limiting membrane in naïve diabetic macular edema: The VITAL Study.

PURPOSE: We aimed to investigate biomarkers and predictive factors for visual and anatomical outcome in patients with naïve diabetic macular edema (DME) who underwent small gauge pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling as a first line treatment. DESIGN: Multicenter, retrospective, interventional study. PARTICIPANTS: 120 eyes from 120 patients with naïve DME treated with PPV and ILM peeling with a follow up of 24 months. METHODS: Change in baseline best corrected visual acuity (BCVA) and central subfoveal thickness (CST) 1, 6, 12 and 24 months after surgery. Predictive value of baseline BCVA, CST, optical coherence tomography (OCT) features (presence of subretinal fluid (SRF) and photoreceptor damage), and time between DME diagnosis and surgery. Additional treatment for DME needed. Intra- and post-operative complications (cataract rate formation, increased intraocular pressure). MAIN OUTCOME MEASURES: The correlation between baseline characteristics and BCVA response (mean change from baseline; categorized improvement ≥5 or ≥10; Early Treatment Diabetic Retinopathy Study (ETDRS) letters) 12 and 24 months after surgery. RESULTS: Mean BCVA was 0.66 ± 0.14 logMAR, 0.52 ± 0.21 logMAR, and 0.53 ± 0.21 logMAR (p<0.001) at baseline, 12 and 24 months, respectively. Shorter time from DME diagnosis until PPV (OR: 0.98, 95% CI: 0.97-0.99, p<0.001) was a predictor for good functional treatment response (area under the curve 0.828). For every day PPV is postponed, the patient's chances to gain ≥5 letters at 24 months decrease by 1.8%. Presence of SRF was identified as an anatomical predictor of a better visual outcome, (OR: 6.29, 95% CI: 1.16-34.08, p = 0.033). Safety profile was acceptable. CONCLUSIONS: Our results reveal a significant functional and anatomical improvement of DME 24 months after primary PPV, without the need for additional treatment. Early surgical intervention and presence of SRF predict good visual outcome. These biomarkers should be considered when treatment is chosen.

Progression of diabetic retinopathy severity after treatment with dexamethasone implant: a 24-month cohort study the 'DR-Pro-DEX Study'.

PURPOSE: Intravitreal anti-vascular endothelial growth factor agents have been shown to reduce diabetic retinopathy (DR) progression; data on the effects of intravitreal corticosteroids on modifying disease severity are limited. This study evaluates the long-term effect of intravitreal dexamethasone implant (DEX) on the severity and progression of non-proliferative DR (NPDR). METHODS: This was a retrospective cohort study. Sixty eyes from 60 consecutive patients with NPDR and diabetic macular edema (DME) treated with dexamethasone implant (DEX group) and 49 eyes from consecutive 49 patients without DME requiring observation only. Fundus angiography images from baseline and after 24 months were graded by two masked assessors into mild, moderate and severe NPDR and PDR, according to the ETDRS classification. Patients were followed up 1-3 and 4-6 months after each DEX implant. Re-treatment with DEX implant was on a pro re nata basis. Records were reviewed for performance of panretinal photocoagulation. Main outcome was as follows: change of DR ≥ 1 grade and progression to proliferative diabetic retinopathy (PDR). RESULTS: Three eyes (5%) in the DEX group and 43 (87.8%) eyes in the control group progressed to PDR (P < 0.0001). Twenty-five eyes (41.7%) in the DEX group but none in the control group demonstrated an improvement in DR severity (P < 0.0001). CONCLUSION: This study provides the first long-term evidence that DEX implant has the potential to not only delay progression of DR and PDR development, but may also improve DR severity over 24 months. Better understanding of the effects of corticosteroids will help guide its use in the treatment pathway of DR.