Current role of intravitreal injections in Irvine Gass syndrome-CRIIG study.

OBJECTIVE: To analyze the role of intravitreal anti-vascular endothelial growth factor (anti-VEGF) or steroid injection for the management of Irvine Gass syndrome. METHODS: It is an interventional, retrospective, multicenter study. One hundred and thirty-two injections were given in 79 eyes of 72 patients with Irvine Gass syndrome. Patients were treated with at least one intravitreal injection of either anti-VEGF or steroid. Outcomes were measured at 12 months (± 1 week). [Ranibizumab (Lucentis; Genentech, South San Francisco, CA) (Razumab; Intas Pharmaceutical Ltd, Ahmedabad, India) Bevacizumab (Avastin; Genentech, South San Francisco, CA) or Aflibercept (Eylea; Regeneron, Tarrytown, NY)] or steroids [Dexamethasone implant (Ozurdex, Allergan Inc, Irvine, CA) or intravitreal triamcinolone)]. RESULTS: Intravitreal injections were initiated in (67.6%) of eyes within 14 weeks of diagnosis. Intravitreal dexamethasone implant was used as the initial intravitreal therapy in (73.4%) of eyes. More than fifty percent (54.5%) of the patients were switched from anti-VEGF to Intravitreal dexamethasone implant. Reduction in the mean CMT was 336.7 ± 191.7 and 160.1 ± 153.1 microns in eyes treated within four weeks and more than 14 weeks from diagnosis (p = 0.005). Mean ETDRS letter gain was 16.7 ± 12.9 and 5.2 ± 9.2 in eyes treated within 4 weeks and more than 14 weeks from diagnosis (p = 0.004). Three eyes injected with intravitreal dexamethasone implant reported an intraocular pressure spike of > 25 mmHg which was controlled with topical medications. No other ocular or systemic adverse events were observed. CONCLUSION: Study results suggest that physicians tend to introduce intravitreal therapy within 14 weeks of diagnosis. The most common therapy at initiation and for the switch is intravitreal dexamethasone implant. Patients treated early (within 4 weeks) respond better in terms of structure and function.

SAFETY OF INTRAVITREAL DEXAMETHASONE IMPLANT (OZURDEX): The SAFODEX study. Incidence and Risk Factors of Ocular Hypertension.

PURPOSE: To analyze the incidence, risk factors, and time course of intraocular pressure elevation after intravitreal dexamethasone implant (Ozurdex). METHODS: The medical charts of 421 consecutive eyes (361 patients) receiving one or more Ozurdex implant between October 2010 and February 2015 were reviewed retrospectively. Ocular hypertension was defined as intraocular pressure of at least 25 mmHg or an increase of at least 10 mmHg from baseline. The main indications for treatment were retinal vein occlusion (34%), diabetic macular edema (30%), postsurgical macular edema (17%), uveitis (14%), and other etiologies (5%). RESULTS: Among 1,000 intravitreal injections, ocular hypertension was recorded for 28.5% of injected eyes over a mean follow-up period of 16.8 months (3-55). Intraocular pressure-lowering medication was required for 31% of eyes. Only three eyes with preexisting glaucoma required filtering surgery to manage postinjection intraocular pressure elevation. Early retreatment between the third and fourth month does not increase the risk of intraocular pressure elevation. Younger age, male sex, Type 1 diabetes, preexisting glaucoma treated with dual or triple therapy, and a history of retinal vein occlusion or uveitis were significant risk factors for ocular hypertension after dexamethasone implant injection (P < 0.05 for all the above). CONCLUSION: Episodes of ocular hypertension after Ozurdex implant were generally transient and successfully managed with topical treatment. An analysis of the risk factors may help to determine the risk-benefit ratio for individual patients treated with dexamethasone implants.

REAL-LIFE STUDY IN DIABETIC MACULAR EDEMA TREATED WITH DEXAMETHASONE IMPLANT: The Reldex Study.

PURPOSE: To evaluate the efficacy and safety of intravitreal implant of dexamethasone (Ozurdex) in diabetic macular edema in real-life practice. METHODS: In this bicentric retrospective study, the authors reviewed 128 eyes of 89 patients. Main outcome measures included changes in best-corrected visual acuity, central macular thickness, time to retreatment, and incidence of adverse effects. Linear mixed-effects models were used to study changes in best-corrected visual acuity and central macular thickness over the 3-year follow-up. RESULTS: Best-corrected visual acuity increased by a mean of 3.6 letters at Month 2 (P = 0.005), 4.2 letters at Month 12 (P = 0.006), 5.3 at Month 24 (P = 0.007), and 9.5 letters at Month 36 (P = 0.023). The proportion of eyes achieving at least a 15-letter improvement from baseline was 25.4% at Month 36. Central macular thickness decreased from 451 µm to 289 µm at Month 2 (P < 0.001), 370 µm at Month 12 (P < 0.001), 377 µm at Month 24 (P = 0.004), and 280 µm at Month 36 (P = 0.001). A mean of 3.6 injections were administered over the 3-year follow-up. Ten percent of eyes developed a transient increase in intraocular pressure (IOP ≥ 25 mmHg), and cataract was removed from 47% of phakic eyes. CONCLUSION: This large case series study showed favorable 3-year outcomes when using Ozurdex to treat diabetic macular edema. Intravitreal Ozurdex provides substantial long-term benefits in the treatment of diabetic macular edema in real-life.

20-year assessment of metastatic latency and subsequent time to death after proton therapy for uveal melanomas.

The aim of this study was to evaluate metastatic latency and survival after the occurrence of metastases in patients with choroidal/ciliary body melanoma treated with proton therapy. This was a retrospective cohort study. All consecutive patients with choroidal/ciliary body melanoma treated with proton therapy between 1991 and 2010 were included. Overall survival, specific survival (SS), local recurrence-free interval, and metastasis-free interval (MFI) were calculated. There were 508 patients. The mean follow-up was 239.4 months. Overall survival and SS rates were 57.2 and 67.6% at 10 years. Pre-equatorial tumor location, advanced tumor stage, and initial exudative retinal detachment were associated independently with SS. Thirty-three percent of the patients (n = 169) had metastases. Local recurrence-free interval and MFI were 91.3 and 65.7% at 10 years, respectively. MFI was shorter in pre-equatorial, large tumors, and/or tumors with exudative retinal detachment. After the occurrence of metastases, the median survival time was 1.25 years and survival probabilities were 62.1% at 1 year, 26.0% at 2 years, and 6.0% at 5 years. Except for age, none of the baseline clinical factors was associated with survival after metastasis occurrence. SS after metastasis occurrence was longer for metastasis occurring more than 10 years after tumor diagnosis (P =0.010). Death after metastasis is independent of initial tumor characteristics. Small tumors still have a risk for metastases after 10 years. Thus, lifelong follow-up is necessary for uveal melanoma patients. Larger series of metastatic patients are needed to evaluate aggressive multimodal treatments of metastases. Death after metastasis is independent of the initial tumor characteristics. Small tumors contraintuitively have a long-life risk of metastases. MFI is associated independently with pre-equatorial location, tumor stage, and retinal detachment.

Incidence of Irvine Gass Syndrome after Phacoemulsification with Spectral-Domain Optical Coherence Tomography.

Purpose: Incidence of significant and non-significant macular edema found using spectral-domain optical coherence tomography (SD-OCT) following cataract surgery.Methods: Prospective, cohort series conducted at the Croix Rousse University Hospital. Significant macular edema (SME) was defined as the presence of fluid with an increase of 30% or more in central subfield macular thickness compared to baseline on SD-OCT at 6 weeks and non-significant macula edema (NSME) as an increase of less than 30%.Results: Nine hundred and twenty-eight eyes in 638 patients were included in the study. Incidence of Irvine Gass (IG) syndrome was 9%, 2.3% of patients presented SME, 6.8% NSME. Epiretinal membrane, diabetes, and capsular rupture were significantly associated with a risk of IG. The risk of developing IG in the fellow eye was 23% in cases of IG in the first eye. In total 8.4% of all included patients developed chronic IG (duration of more than 6 months).Conclusion: This study reports the incidence of IG during 6 months of surgical activity at a French university hospital center.

First-line treatment algorithm and guidelines in center-involving diabetic macular edema.

Management of center-involving diabetic macular edema represents a real therapeutic challenge. Diabetic macular edema is the leading cause of visual acuity impairment in diabetic patients. Since the advent of intravitreal drugs, management of diabetic macular edema has significantly evolved. The historical grid laser photocoagulation is no longer recommended as first-line treatment of diabetic macular edema owing to the findings of the pivotal randomized controlled trials, and anti-vascular endothelial growth factor therapy has emerged as first-line therapy. Steroids also represent a valid treatment option in the management of naïve diabetic macular edema and their efficacy has also been confirmed in several studies. The optimal treatment for diabetic macular edema should consider both general and ophthalmological comorbidities. Patient compliance and motivation should also be carefully evaluated as some treatments require monthly follow-up. Based on recent literature evidence, the present review provides clinicians with a first-line treatment algorithm for center-involving diabetic macular edema tailored to the patient's individual characteristics.

Pharmacological Management of Diabetic Macular Edema in Real-Life Observational Studies.

OBJECTIVES OF THE STUDY: of observational studies concerning the pharmacological management of diabetic macular edema (DME). METHODS: A literature review was conducted using the PubMed database on 1 February 2018 to identify studies evaluating the efficacy of anti-VEGF and dexamethasone (DEX) implants for DME. Studies with more than 10 patients and follow-up of more than 6 months were selected. Analyses were carried out on the overall population and on subgroups defined according to baseline visual acuity (BVA) and the patients' naïve or non-naïve status. RESULTS: Thirty-two studies evaluating the efficacy of anti-VEGF and 31 studies evaluating the efficacy of DEX-implants were retained, concerning 6,842 and 1,703 eyes, respectively. A mean gain of +4.7 letters for a mean of 5.8 injections (mean follow-up: 15.6 months) and +9.6 letters for a mean of 1.6 injections (10.3 months) was found in the anti-VEGF and DEX-implant studies, respectively. Final VA appears to be similar for both treatment (62 letters for anti-VEGF, 61.2 letters for DEX-implant), and BVA appears lower for DEX-implant, which may partially explain the greater visual gain. The DEX-implant studies show greater gains in VA compared to the anti-VEGF studies, especially for higher BVA. Indeed, mean gains for the subgroups of patients with BVA<50 letters, 5060 letters are +4.3, +5.8, and +3.1 letters, respectively, in the anti-VEGF studies and +10.5, +9.3, and +8.8 letters, respectively, in the DEX-implant studies. Regarding the patient's initial status, only naïve status appears to confer the best functional response in DEX-implant studies. CONCLUSION: Observational studies investigating DEX-implant report clinically similar final VA when compared to anti-VEGF, but superior visual gains in real-life practice. This latter difference could be due to the better BVA, but also to the fact that less injections were administered in the anti-VEGF observational studies than in the interventional studies.

The Pattern of Recurrence in Diabetic Macular Edema Treated by Dexamethasone Implant: The PREDIAMEX Study.

PURPOSE: To assess the time to functional and anatomic recurrence of macular edema (ME) after a first intravitreal dexamethasone implant in eyes with diabetic macular edema (DME). DESIGN: A 6-month observational, prospective, uncontrolled, multicenter, national case series. PARTICIPANTS: Thirty-seven patients included between January 2015 and June 2016. METHODS: Patients were monitored at baseline and then monthly over 6 months after the first treatment. MAIN OUTCOME MEASURES: Different patterns of recurrence were defined: qualitative and quantitative anatomic recurrences and functional recurrence. RESULTS: Median ME duration before the first dexamethasone implant was 2.04 months. All patients received a dexamethasone implant for the first time, but 73% of patients had not undergone any form of treatment previously. The mean time from baseline to qualitative anatomic, quantitative anatomic, and functional recurrence was 4.22 months (95% confidence interval [CI], 3.80-4.65 months), 4.73 months (95% CI, 4.34-5.12 months), and 4.89 months (95% CI, 4.53-5.26 months), respectively. Almost all patients (7/8) who demonstrated a qualitative anatomic recurrence showed a subsequent quantitative anatomic and functional recurrence days later. Mean improvement in best-corrected visual acuity was 10.1 letters (95% CI, 6.7-13.4 letters) and 7.3 letters (95% CI, 4.1-10.6 letters) at months 2 and 6, respectively. The mean reduction in central subfield macular thickness was 206 µm (95% CI, 157-255 µm) and 146 µm (95% CI, 98-195 µm) at months 2 and 6, respectively. CONCLUSIONS: Dexamethasone implant is a functionally and anatomically effective treatment for DME in real-life practice. Qualitative anatomic recurrence seems to be an early sign of quantitative anatomic and functional recurrence. Further studies should demonstrate if early retreatment at the qualitative anatomic recurrence stage could better protect patient visual function.

Correlation in retinal nerve fibre layer thickness in uveitis and healthy eyes using scanning laser polarimetry and optical coherence tomography.

PURPOSE: To evaluate the correlation of retinal nerve fibre layer (RNFL) thickness measured using spectral domain optical coherence tomography (SD-OCT) and scanning laser polarimetry (SLP) in uveitic eyes compared with healthy eyes. METHODS: A descriptive, observational, prospective, consecutive, cross-sectional, controlled, monocentre case series was conducted from May to October 2015. Clinical characteristics, best-corrected visual acuity, intraocular pressure, RNFL thickness measurement with SD-OCT and SLP using GDx variable corneal compensation (GDx VCC) were performed for each patient. An evaluation of anterior chamber inflammation with laser flare-cell meter was also carried out. Correlations between SD-OCT and GDx VCC RNFL measurement were evaluated by linear regression analysis. RESULTS: Fifty-four patients were included and divided into two groups: 50 healthy eyes in 29 patients and 42 uveitic eyes in 25 patients. The mean RNFL thickness was 98.08(±8.42) and 113.21(±20.53) µm in the healthy group and the uveitic group, respectively, when measured with SD-OCT (p<0.001); and 56.43(±5.24) and 58.77(±6.67) µm, respectively, when measured with GDx VCC (p=0.078). There was a strong correlation between total average RNFL thickness measured using SD-OCT and GDX (r=0.48, p<0.001) in healthy eyes but there was no correlation in the uveitic eyes (r=0.2, p=0.19). CONCLUSIONS: RNFL thickness was significantly greater when measured using SD-OCT in active uveitis as compared with GDx. There was no correlation between the RNFL thickness measurements obtained using the two techniques in uveitic eyes. The discrepancies between the results suggest that for these patients both techniques should be used in conjunction to obtain an accurate measurement of RNFL. TRIAL REGISTRATION NUMBER: IRB 00008855 Société Française d'Ophtalmologie IRB#1.

Effectiveness and safety of dexamethasone implants for postsurgical macular oedema including Irvine-Gass syndrome: the EPISODIC-2 study.

AIM: To assess the effectiveness of intravitreal dexamethasone implants for treating postsurgical macular oedema (PSMO) including Irvine-Gass syndrome and determining the predictive factors of treatment response. METHODS: Descriptive, observational, retrospective, consecutive, uncontrolled, multicentre, national case series. One hundred patients were included between April 2011 and June 2014, with a minimum of 1-year follow-up. Patients received dexamethasone implant 0.7 mg at baseline. Clinical characteristics, best-corrected visual acuity (BCVA), central subfield macular thickness (CSMT) and intraocular pressure were measured at each visit. The main outcome measure was the change in BCVA (Early Treatment of Diabetic Retinopathy Study (ETDRS) letters: L). An analysis of predictive factors of treatment response is also provided. RESULTS: Mean improvement in BCVA was 9.6 (±10.6) L at month 6 and 10.3 (±10.7) L at month 12 (p<0.001). The proportion of eyes with gains in BCVA of 15 or more letters was 32.5% and 37.5% at months 6 and 12, respectively. The mean reduction in CSMT was 135.2 and 160.9 µm at months 6 and 12, respectively (p<0.001). Thirty-seven per cent of patients did not need a second injection after the first injection during follow-up. The presence of at least one PSMO risk factor decreases the probability of a gain in visual acuity (VA) ≥10 L (p=0.006). Initial VA ≤50 L at baseline and non-naïve status decrease the probability of having only one injection during follow-up (p=0.044). CONCLUSIONS: The significant gain in BCVA from baseline achieved at month 6 was maintained at month 12 after intravitreal injection of dexamethasone implant. Naïve status seems to be a good predictive factor of treatment response.

Uveitis: Diagnostic work-up. A literature review and recommendations from an expert committee.

PURPOSE: Diagnosis of uveitis is difficult. Etiologic investigations should take into account the epidemiology of uveitis and should focus on the most severe forms of the disease and those which can be treated. This study was undertaken to establish recommendations for the diagnosis of uveitis. METHODS: Recommendations were developed by a multidisciplinary panel of 14 experts, including internists, ophthalmologists, and rheumatologists, and are based on a review of the literature and the results of the ULISSE study, which was the first prospective study to assess the efficacy of a standardized strategy for the etiologic diagnosis of uveitis. The following groups of patients are not included in these recommendations: children, immunocompromised patients, patients with severe retinal vasculitis, and those with specific eye diseases diagnosed by ophthalmologic examination only. RESULTS: Diagnosis should be guided by the medical history of the patient and physical examination. Serologic screening for syphilis is appropriate in all forms of uveitis. If uveitis is not diagnosed at this stage, investigations oriented by the anatomic characteristics of uveitis are proposed. These consist of assays for HLA-B27 (in unilateral acute anterior non-granulomatous uveitis), serum angiotensin-converting enzyme, interferon-gamma release, chest computed tomography (chronic uveitis), cerebral magnetic resonance imaging and anterior chamber tap with interleukin-10 analysis (intermediate or posterior uveitis in patients >40years-old). Other investigations prescribed in the absence of orientation are usually unhelpful. CONCLUSIONS: A strategy is proposed for the etiologic diagnosis of uveitis. The benefit of more invasive investigations remains to be determined.

Effectiveness and safety of dexamethasone implants for post-surgical macular oedema including Irvine-Gass syndrome: the EPISODIC study.

AIM: To assess the effectiveness and safety of intravitreal dexamethasone implants for treating post-surgical macular oedema, including Irvine-Gass syndrome refractory to first-line treatments. METHODS: Descriptive, observational, retrospective, consecutive, uncontrolled, multicentre, national case series. 50 patients were included in the study between March 2011 and June 2013 with a minimum 6 months follow-up. At baseline, each patient received a dexamethasone implant 0.7 mg (Ozurdex). Best-corrected visual acuity (BCVA), central subfield macular thickness (CSMT), and intraocular pressure (IOP) were measured at baseline and then monthly. The main outcome measure was the mean change in BCVA (in ETDRS letters (Early Treatment Diabetic Retinopathy Study): L) RESULTS: Baseline mean±SD BCVA was 55.7±15.4 L. At month 2, BCVA was 71.8±10.5 L and 61.2% of patients had an increase of more than 15 letters. Baseline mean CSMT was 544±117.2 µm and this decreased to 302 µm at month 2. Anatomic and functional recurrences were both first detected from month 3 and continued throughout follow-up, with values consistently above baseline. The peak in IOP was reached in month 1 with mean IOP of 15.3±4.6 mm Hg. Of the 39/50 patients followed up for 12 months, 49% received a second injection. The anatomic and functional response and safety patterns were similar to that obtained with the first intravitreal injection, demonstrating Ozurdex's reproducibility. However, more than half of the patients followed-up for at least 1 year presented neither functional nor anatomical recurrence. CONCLUSIONS: Ozurdex would appear to be an interesting alternative therapy for treating post-surgical macular oedema, including Irvine-Gass syndrome refractory to first-line treatments.