Ranibizumab For Diabetic Macular Edema Research Articles

Systemic Associations with Residual Subretinal Fluid after Ranibizumab in Diabetic Macular Edema.

Purpose To investigate the impact of systemic diseases on the occurrence of subretinal fluid (SRF) in diabetic macular edema (DME) and prognostic factors for residual SRF following three consecutive monthly intravitreal ranibizumab. Methods Ninety-seven eyes from 68 patients with DME who completed 3 consecutive monthly injections of ranibizumab were enrolled. Systemic parameters mainly included chronic kidney disease (CKD), hypertension, HbA1c, and insulin dependence. Renal parameters for CKD were serum creatinine, estimated glomerular filtration rate (eGFR), and serum albumin. Ocular factors were baseline central macular thickness (CMT), severity of diabetic retinopathy (DR), and status of panretinal photocoagulation (PRP). Results Chronic kidney disease had significant correlation with baseline SRF (R = 0.397, p < 0.001 after partial correlation with adjustment for age and DR severity). As for CKD, lower serum albumin, but not eGFR or serum creatinine, was associated with baseline presence of SRF (p = 0.026, p = 0.08 and p = 0.53, resp., after adjustment for age and DR severity). Overall, lower eGFR and lower HbA1c values, contrary to popular belief, predicted the presence of residual SRF following intravitreal injections (p = 0.016 and p < 0.001, resp.). Conclusions Tight sugar control and poorer baseline kidney function may slow the resorption of SRF after anti-VEGF injections in patients with DME in the short term.

Ranibizumab in Diabetic Macular Oedema - A Benefit-risk Analysis of Ranibizumab 0.5 mg PRN Versus Laser Treatment.

Introduction: The structured Benefit–risk Action Team (BRAT) approach aims to assist healthcare decision makers in treatment assessments. We applied BRAT to compare the benefit–risk profile of ranibizumab 0.5 mg versus laser photocoagulation for the treatment of diabetic macular oedema (DMO). Methods: One-year data for the ranibizumab 0.5 mg pro re nata (PRN) and laser arms of the phase III trials RESPOND (NCT01135914; n=220), RESTORE (NCT00687804; n=345), and REVEAL (NCT00989989; n=396) were included in the analysis. The benefit measures included ≥10 letters gain/avoidance of loss in best-corrected visual acuity (BCVA), achieving central retinal thickness (CRT) <275 μm, and 25-item Visual Function Questionnaire (VFQ-25) outcomes. The risks measures included endophthalmitis, intraocular pressure increase, hypertension, proteinuria, arterial/venous thromboembolic events and deaths. Results: Ranibizumab treatment provided significant benefits compared with laser for ≥10 letter BCVA gain at month 12 (387/1,000 versus 152/1,000 patients), CRT <275 μm at 12 months (474/1,000 versus 348/1,000 patients), and improvement of ≥6.06 on the VFQ-25 near activities subscale (325/1,000 versus 245/1,000 patients). Results for the risk measures were similar for both treatments. Conclusions: Superior clinically relevant outcomes were observed with ranibizumab 0.5 mg PRN compared with laser without compromising on safety. This analysis further supports the positive benefit–risk profile of ranibizumab 0.5 mg PRN.

The United Kingdom Diabetic Retinopathy Electronic Medical Record Users Group, Report 1: baseline characteristics and visual acuity outcomes in eyes treated with intravitreal injections of ranibizumab for diabetic macular oedema

AimsTo describe baseline characteristics and visual outcome for eyes treated with ranibizumab for diabetic macular oedema (DMO) from a multicentre database.MethodsStructured clinical data were anonymised and extracted from an electronic...

Vitreoretinal interface abnormalities in patients treatedwith ranibizumab for diabetic macular oedema

PurposeIntravitreal anti-vascular endothelial growth factor (VEGF) agents are effective in the treatment of central involving diabetic macular oedema (DMO). Vitreoretinal interface abnormalities (VRIA) are common in patients with DMO, and the effect of these on the response to anti-VEGF treatment is unclear. Furthermore the effect of anti-VEGF agents on the VRIA itself is uncertain.MethodProspective study of consecutive patients treated with ranibizumab (RZB) for DMO as part of routine clinical care in one eye unit over a 1-year period. Visual acuity (Va), central retinal thickness (CRT) and injection frequency data was recorded on an electronic database. Treatment was initiated with four monthly RZB injections and then a monthly PRN regime. All patients underwent high-density spectral-domain optical coherence tomography (SDOCT) at baseline and 12 months. The SDOCTs were graded by two observers masked to the outcome.ResultsOne hundred and four eyes (77 patients) were included in the analysis. The mean age was 62 years, and 62% were male. The mean presenting vision was 62 letters and CRT 472 μm. Eighty eyes retained stable Va, and 17 had an improvement in Va. At baseline, 39 eyes had associated focal vitreomacular adhesion (VMA) and by 12 months this reduced to 30 (p = 0.04), with 12 releasing VMA and three developing it. Patients with VMA had significantly better final Va than those without VMA. Improvement in CRT was greatest in those where VMA released during the study. Forty-five eyes had some degree of foveal involving epiretinal membrane (ERM) at baseline, and 28 were considered to have clinically significant ERM. There was no clinically relevant change in ERM during the study. Patients with significant ERM at baseline had a lower final vision. Multivariate analysis showed that ERM and more severe retinopathy at baseline were predictive of less visual improvement (p < 0.01). Shorter intraretinal cyst length, ERM and the absence of VMA at baseline were predictive of a worsened anatomical response (p < 0.001).ConclusionVRIA are related to outcome in patients treated with RZB. ERM was associated with a worsened visual and anatomic response, and VMA with an improved anatomical response particularly when spontaneous VMA release occurred during treatment. The presence and severity of ERM was not affected by RZB treatment.

Outcomes after a 1-Year Treatment with Ranibizumab for Diabetic Macular Edema in a Clinical Setting

Purpose: The aim of this study was to assess the efficacy and safety of ranibizumab in patients with diabetic macular edema (DME). Methods: We conducted a retrospective analysis of consecutive patients with vision loss due to DME who were treated with ranibizumab. All patients received a loading dose of 3 monthly injections followed by re-treatments on an as-needed basis. The primary endpoint was the change in best-corrected visual acuity (BCVA) at 12 months. Secondary endpoints were the change in central retinal thickness (CRT) and the number of intravitreal injections (IVI) at 12 months. Results: One hundred and six eyes of 78 patients were included. BCVA changed from 48.3 (20/100) letters at baseline to 59.0 letters (20/63) at 12 months (p < 0.0001; mean gain: +10.7 letters), and 38% of the patients had a final BCVA >70 letters. CRT decreased from 519 µm at baseline to 355 µm at 12 months (p < 0.0001). The threshold of the first quartile of the baseline VA was 40 letters. Patients with a baseline VA >40 letters had a higher final VA of 66 ± 14 letters (20/50) versus 43 ± 18 letters (20/125) for patients with a baseline VA ≤40 letters (p < 0.0001). A mean number of 5.4 (3-10) IVI were administered. Conclusion: This study conducted in a clinical setting confirms the results of previous randomized trials. The final BCVA was mainly influenced by the baseline BCVA, which supports the utility of early DME treatment before patients experience a severe vision loss.

Association of Circulating Markers With Outcome Parameters in the Bevacizumab and Ranibizumab in Diabetic Macular Edema Trial.

The purpose of this study was to evaluate selected candidate biomarkers as potential markers for patients with diabetic macular edema (DME) who receive antivascular endothelial growth factor (VEGF) therapy. Selected biomarkers included blood levels of messenger RNA (mRNA) of retinoschisin, RPE65, rhodopsin, and endothelial progenitor cell markers CD34 and CD133. Blood samples were obtained from 89 patients with DME according to the study protocol of the Bevacizumab and Ranibizumab in Diabetic Macular Edema (BRDME) study. During each monthly visit, patients underwent optical coherence tomography scanning and visual acuity was measured. Anti-VEGF injections were administered at fixed monthly intervals over 6 months. Analyses of covariance using simplified and linear mixed models were used to examine the correlations between candidate markers and changes in visual acuity and central subfield thickness. Plasma mRNA levels of retinoschisin were negatively associated with visual acuity, and plasma mRNA levels of rhodopsin were positively associated with visual acuity in patients with DME (P < 0.01 and P < 0.05, respectively). In addition, changes in central subfield thickness between baseline and months 1, 2, and 3 during anti-VEGF treatment were associated with mRNA levels of retinoschisin, rhodopsin, and the ratio of retinoschisin-to-rhodopsin (P < 0.01, all). This prospective, multicenter study found that circulating mRNA levels of retinoschisin and rhodopsin are associated with visual acuity and changes in central subfield thickness during anti-VEGF therapy in patients with DME. (ClinicalTrials.gov number: NCT01635790.).

Early and Long-Term Responses to Anti–Vascular Endothelial Growth Factor Therapy in Diabetic Macular Edema: Analysis of Protocol I Data

To determine whether early visual acuity response to ranibizumab in diabetic macular edema is associated with long-term outcome. Post hoc analysis of randomized controlled trial data. Pooled data from the ranibizumab plus prompt and deferred laser treatment arms of the Diabetic Retinopathy Clinical Research Network's Protocol I study were used to explore the relationship between early (week 12) and late (weeks 52-156) visual acuity response (mean change from baseline in best-corrected visual acuity [CFB BCVA]; categorized improvement [<5, 5-9, or ≥10 Early Treatment Diabetic Retinopathy Study (ETDRS) letters] in BCVA). In the analysis population (340 eyes), <5-, 5- to 9-, and ≥10-letter BCVA improvements occurred in 39.7%, 23.2%, and 37.1% of eyes, respectively, at 12weeks, and 34.2%, 16.5%, and 49.3% of eyes at 156weeks. Within each early BCVA response category (<5, 5-9, and ≥10 letters of improvement at 12weeks), mean CFB BCVA at 52-156weeks varied by <5 letters from that at 12weeks. CFB BCVA and <5-letter improvement at 12weeks showed significant positive and negative association, respectively, with CFB BCVA and ≥10-letter improvement at 52 and 156weeks. Similar relationships were demonstrated in eyes with baseline BCVA <69 letters, and associations remained significant after multivariate adjustment for potential confounders. Ranibizumab ± laser therapy resulted in similar rates (∼40%) of suboptimal (<5-letter) and pronounced (≥10-letter) BCVA improvement at 12weeks. Eyes with suboptimal early BCVA response showed poorer long-term visual outcomes than eyes with pronounced early response (mean improvement 3.0 vs 13.8 letters at 156weeks).

Real-World Outcomes of Ranibizumab Treatment for Diabetic Macular Edema in a United Kingdom National Health Service Setting

To determine visual acuity (VA) and spectral-domain optical coherence tomography (OCT) outcomes with intravitreal ranibizumab for diabetic macular edema (DME) in a United Kingdom National Health Service clinical setting. Retrospective interventional case series. Consecutive patients with DME, treated with the first ranibizumab injection between August 2013 and March 2014 across 4 sites of Moorfields Eye Hospital, London. Two hundred eyes of 164 consecutive patients with center-involving DME and VA ≤79 ETDRS letters, central subfield macular thickness (CST) ≥350μm on Topcon 3D OCT 2000, initiated on a loading phase of 3 intravitreal ranibizumab injections and who had at least 6months follow-up were reviewed. Subsequent retreatment was guided by VA and OCT with the aim of treating to stability. VA, OCT CST, and macular volume (MV) were recorded at baseline and monthly to 12months. The mean VA, mean CST, and mean MV at baseline were 54.4 (± 15.26) letters, 490.16 (± 116.54) μm, and 10.46 (± 2.28) mm3. The mean VA change at 12months was+6.6 (± 13.35) letters (P= .0003). A total of 40.3% of patients (n= 77) gained ≥10 letters and 25.1% (n= 48) gained ≥15 letters; 8.9% (n= 17) lost ≥10 letters and 6.3% (n= 12) lost ≥15 letters. At 12months, the mean change in CST and MV were-133.9 (± 160.12) μm (P= .0001) and-1.5 (± 1.96) mm3 (P= .0001), respectively. An average of 7.2 (± 2.3) injections were given over 12months. Outcomes with 3 loading injections of 0.5mg ranibizumab given monthly followed by pro re nata retreatment in a clinical setting are comparable with outcomes from clinical trials.

Intravitreal ranibizumab for diabetic macular oedema in previously vitrectomized eyes.

There is little information about the efficacy of intravitreal vascular endothelial growth factor (VEGF) inhibition in vitrectomized eyes. This study aimed to evaluate the efficacy of anti-VEGF (ranibizumab) on diabetic macular oedema in previously vitrectomized eyes. A nationwide retrospective review of medical records from 2010 to 2013. We identified 33 previously vitrectomized eyes in 28 patients treated with ranibizumab injections for diabetic macular oedema. Median follow-up was 323days (interquartile range 72-1404days). Baseline mean visual acuity was 0.57 logMAR (95% CI 0.13-1.01) before injections. After an average of 4.7 injections (range 1-15), mean visual acuity remained stable at 0.54 logMAR (95% CI 0.13-0.95) with a mean improvement of 0.03 (p=0. 45, 95% CI -0.12 to 0.06). In 12 eyes (36%), visual acuity improved 0.1 logMAR or more, in 12 eyes (36%), vision was unchanged (gain or loss of 0-0.05 logMAR), and in nine eyes (27%), vision decreased 0.1 logMAR or more. Mean central foveal thickness (CFT) on optical coherence tomography (OCT) scan was 412μm (95% CI 390-434μm) before injections. After injections, the mean CFT decreased to 352μm (95% CI 334-370μm). The mean reduction in CFT was 14% (95% CI 4-24%, p=0.01). Sixteen eyes (48.5%) became devoid of oedema on the last OCT scan. Despite the significant reduction in CFT, the visual acuity remained unchanged. Intravitreal ranibizumab can be effective in previously vitrectomized eyes with diabetic macular oedema. However, the response is variable and should be carefully monitored.

Comparison of the Effectiveness of Intravitreal Ranibizumab for Diabetic Macular Edema in Vitrectomized and Nonvitrectomized Eyes

Purpose: To compare the effectiveness of intravitreal ranibizumab (IVR) for diabetic macular edema (DME) between eyes with and without previous vitrectomy. Procedures: We prospectively assessed the best-corrected visual acuity (BCVA) and central macular thickness (CMT) after IVR for 6 months. Results: There were no significant differences in the baseline BCVA and CMT between both groups. In the nonvitrectomized group (n = 15), the mean changes of BCVA and CMT from baseline to month 6 were significant (p < 0.01). In the vitrectomized group (n = 10), the improvement appeared to be slower, and the mean BCVA improvement was not significant (p = 0.5), although the mean CMT decrease was significant (p < 0.05). There were no significant differences in the mean changes of BCVA and CMT between both groups at 6 months. Conclusions: The difference in the effectiveness of IVR between both groups was not significant. IVR can be a treatment option even for vitrectomized DME eyes.

The Impact of Systemic Factors on Clinical Response to Ranibizumab for Diabetic Macular Edema

To evaluate the effect of systemic factors on best-corrected visual acuity (BCVA) achieved with ranibizumab (Lucentis; Genentech, Inc, South San Francisco, CA) for treatment of diabetic macular edema (DME) in the RIDE and RISE phase 3 studies. Exploratory, post hoc analysis of 2 randomized, double-masked, sham-injection controlled studies. Adults with DME, BCVA of 20/40 to 20/320 Snellen equivalent, and central foveal thickness of 275 μm or more. Analysis of RIDE (clinicaltrials.gov identifier, NCT00473382) and RISE (clinicaltrials.gov identifier, NCT00473330) pooled ranibizumab data through month 24. Change in BCVA was assessed for association with the following covariates: age, body mass index (BMI), blood pressure, serum glucose, glycosylated hemoglobin (HbA1c), blood urea nitrogen, serum creatinine, estimated glomerular filtration rate, and blood chemistry variables. Change in BCVA at month 24 was assessed according to the following categories of diabetes medication use history: insulin only (n= 193), insulin plus other medications (n= 221), or other noninsulin medications (n= 331). Change in BCVA from baseline assessed by randomized treatment group in pooled 0.3- and 0.5-mg monthly ranibizumab groups. In patients with DME, vision improvement with ranibizumab was not influenced by systemic factors such as diabetes medication history, serum glucose, HbA1c, renal function, BMI, and blood pressure. Patients taking insulin with or without other medications at baseline had longer diabetes disease duration (mean, 17.4 and 20.9 years, respectively) compared with those taking other noninsulin medications (mean, 11.9 years). At month 24, among ranibizumab-treated patients, the mean BCVA change from baseline (Early Treatment Diabetic Retinopathy Study letters ± standard deviation) was not different between patients taking only insulin (12.6±11.2 letters), insulin plus other medications (12.2±12.4 letters), or other noninsulin medications (14.0±13.7 letters). Mean BCVA change also was comparable among patients taking thiazolidinediones (12.9±9.7 letters) and those not taking thiazolidinediones (13.2±13.3 letters). There were no associations between systemic factors (baseline values or change from baseline) and mean change of BCVA at month 24. These results suggest that visual response to ranibizumab therapy in DME was not influenced by nonocular factors related to systemic management of diabetes in the RIDE and RISE studies.

Clinical study of grid pattern laser photocoagulation with Ranibizumab for diabetic macular edema

Clinical study of grid pattern laser photocoagulation with Ranibizumab for diabetic macular edema

Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema: Two-Year Results from a Comparative Effectiveness Randomized Clinical Trial

To provide 2-year results comparing anti-vascular endothelial growth factor (VEGF) agents for center-involved diabetic macular edema (DME) using a standardized follow-up and retreatment regimen. Randomized clinical trial. Six hundred sixty participants with visual acuity (VA) impairment from DME. Randomization to 2.0-mg aflibercept, 1.25-mg repackaged (compounded) bevacizumab, or 0.3-mg ranibizumab intravitreous injections performed up to monthly using a protocol-specific follow-up andretreatment regimen. Focal/grid laser photocoagulation was added after 6 months if DME persisted. Visits occurred every 4 weeks during year 1 and were extended up to every 4 months thereafter when VA and macular thickness were stable. Change in VA, adverse events, and retreatment frequency. Median numbers of injections were 5, 6, and 6 in year 2 and 15, 16, and 15 over 2 years in the aflibercept, bevacizumab, and ranibizumab groups, respectively (global P= 0.08). Focal/grid laser photocoagulation was administered in 41%, 64%, and 52%, respectively (aflibercept vs. bevacizumab, P < 0.001; aflibercept vs. ranibizumab, P= 0.04; bevacizumab vs. ranibizumab, P= 0.01). At 2 years, mean VA improved by 12.8, 10.0, and 12.3 letters, respectively. Treatment group differences varied by baseline VA (P= 0.02 for interaction). With worse baseline VA (20/50 to 20/320), mean improvement was 18.1, 13.3, and 16.1 letters, respectively (aflibercept vs. bevacizumab, P= 0.02; aflibercept vs. ranibizumab, P= 0.18; ranibizumab vs. bevacizumab, P= 0.18). With better baseline VA (20/32 to 20/40), mean improvement was 7.8, 6.8, and 8.6 letters, respectively (P > 0.10, for pairwise comparisons). Anti-Platelet Trialists' Collaboration (APTC) events occurred in 5% with aflibercept, 8% with bevacizumab, and 12% with ranibizumab (global P= 0.047; aflibercept vs. bevacizumab, P= 0.34; aflibercept vs. ranibizumab, P= 0.047; ranibizumab vs. bevacizumab, P= 0.20; global P= 0.09 adjusted for potential confounders). All 3 anti-VEGF groups showed VA improvement from baseline to 2 years with a decreased number of injections in year 2. Visual acuity outcomes were similar for eyes with better baseline VA. Among eyes with worse baseline VA, aflibercept had superior 2-year VA outcomes compared with bevacizumab, but superiority of aflibercept over ranibizumab, noted at 1 year, was no longer identified. Higher APTC event rates with ranibizumab over 2 years warrants continued evaluation in future trials.

A Crossover Design for Comparative Efficacy: A 36-Week Randomized Trial of Bevacizumab and Ranibizumab for Diabetic Macular Edema

To investigate the comparative efficacy of bevacizumab (Avastin) and ranibizumab (Lucentis; both Genentech, Inc, South San Francisco, CA) for diabetic macular edema (DME) using a crossover study design. Randomized, double-masked, 36-week, 3-period crossover clinical trial. Fifty-six subjects with DME involving the center of the macula in one or both eyes. Monthly intravitreous injections of bevacizumab (1.25 mg) or ranibizumab (0.3 mg). Comparison of mean changes in visual acuity and central retinal thickness, tested using a linear mixed-effects model. Based on the linear mixed-effects model, the 3-month estimated mean improvement in visual acuity was 5.3 letters for bevacizumab and 6.6 letters for ranibizumab (difference, 1.3 letters; P = 0.039). Estimated change in optical coherence tomography (OCT) central subfield mean thickness (CSMT) was -89 μm for bevacizumab and -137 μm for ranibizumab (difference, 48 μm; P < 0.001). Incorporating cumulative treatment benefit, the model yielded a predicted 36-week (9-month) average improvement in visual acuity of 7.1 letters (95% confidence interval [CI], 5.0-9.2) for bevacizumab and 8.4 letters (95% CI, 6.3-10.5) for ranibizumab, and a change in OCT CSMT of -128 μm (95% CI, -155 to -100) for bevacizumab and -176 μm (95% CI, -202 to -149) for ranibizumab. There was no significant treatment-by-period interaction (i.e., treatment difference was constant in all 3 periods), nor was there a significant differential carryover effect from one period to the next. This trial demonstrated a statistically significant but small relative clinical benefit of ranibizumab compared with bevacizumab for treatment of DME, using a markedly reduced sample size relative to a full comparative efficacy study. The effects on visual acuity and central retinal thickness for the 2 drugs are consistent with those reported at 1 year for the concurrent parallel-group trial by the Diabetic Retinopathy Clinical Research Network testing bevacizumab, ranibizumab, and aflibercept for DME. The 3-period crossover design allowed for meaningful and efficient comparison, suggesting that this approach may be useful for future comparative efficacy studies of anti-vascular endothelial growth factor drugs for DME.

Five-Year Outcomes of Ranibizumab With Prompt or Deferred Laser Versus Laser or Triamcinolone Plus Deferred Ranibizumab for Diabetic Macular Edema

To compare long-term vision and anatomic effects of ranibizumab with prompt or deferred laser vs laser or triamcinolone+ laser with very deferred ranibizumab in diabetic macular edema (DME). Randomized clinical trial. Eight hundred and twenty-eight study eyes (558 [67%] completed the 5-year visit), at 52 sites, with visual acuity 20/32 to 20/320 and DME involving the central macula were randomly assigned to intravitreous ranibizumab (0.5mg) with either (1) prompt or (2) deferred laser; (3) sham injection+ prompt laser; or (4) intravitreous triamcinolone (4mg)+ prompt laser. The latter 2 groups could initiate ranibizumab as early as 74weeks from baseline, for persistent DME with vision impairment. The main outcome measures were visual acuity, optical coherence central subfield thickness, and number of injections through 5 years. At 5 years mean (± standard deviation) change in Early Treatment Diabetic Retinopathy Study visual acuity letter scores from baseline in the ranibizumab+ deferred laser (N= 111), ranibizumab+ prompt laser (N= 124), laser/very deferred ranibizumab (N= 198), and triamcinolone+ laser/very deferred ranibizumab (N= 125) groups were 10 ± 13, 8 ± 13, 5 ± 14, and 7 ± 14, respectively. The difference (95% confidence interval) in mean change between ranibizumab+ deferred laser and laser/very deferred ranibizumab and triamcinolone+ laser/very deferred ranibizumab was 4.4 (1.2-7.6, P= .001) and 2.8 (-0.9 to 6.5, P= .067), respectively, at 5 years. Recognizing limitations of follow-up available at 5 years, eyes receiving initial ranibizumab therapy for center-involving DME likely have better long-term vision improvements than eyes managed with laser or triamcinolone+ laser followed by very deferred ranibizumab for persistent thickening and vision impairment.

The relationship between central retinal thickness relative change and visual prognosis in diabetic macular edema patients following intravitreal injection of ranibizumab

Background The studies on intravitreal ranibizumab for diabetic macular edema (DME) primarily focuses on the absolute change of central retinal thickness, while the affection of the relative change of central retinal thickness (RCRT) or relative change of central retinal thickening (RCRTing) on visual prognosis has not been elucidated completely. Objective This study aimed to evaluate the effect of RCRT and RCRTing in assessing visual prognosis in DME patients following intravitreal injection of ranibizumab. Methods A self-controlled observational study was designed.Thirty eyes of thirty patients with clinically significant DME (CSDME) were recruited in Beijing 401 Hospital of China Nuclear Industry from November 2013 to October 2014.Ranibizumab of 0.05 ml (10 mg/ml) was intravitreally injected by 30G syringe needle at 3.5 mm posterior corneal limbus.Best corrected visual acuity (BCVA) far 2.5 meters away modified ETDRs visual chart was examined before injection and 3 and 6 months after injection, and the BCVA difference value between before injection and 6 months after injection was calculated as the absolusion BCVA (ABCVA). Spectral domian optical coherence tomography (SD-OCT) system was employed to measure the central retinal thickness (CRT) and to calculate the RCRT and RCRTing value.The correlations of RCRT or RCRTing with ABCVA was analyzed. Results The LogMAR values were (0.66±0.20), (0.40±0.25)BCVA and (0.37±0.25) before injection and 3, 6 months after injection respectively in the CSDME patients, with a significant difference among them (F=36.79, P<0.05). The values were obviously improved 3 and 6 months after injection compared with before injection (both at P<0.05). The mean ABCVA (LogMar) of the patients was (0.30±0.21). The CRT 3, 6 , pmyjd sgyrt omkrvyopm values were (508.63±130.44), (331.07±71.84) and (311.77±64.47)μm before injection and respectively in the CSDME patients, showing a significant difference among them (F=49.78, P<0.05). The CRT values were evidently reduced 3 and 6 months after injection in comparison with before injection (both at P<0.05), and the mean ACRT value was (196.87±140.59)μm.The ABCVA values were (0.13±0.13), (0.44±0.14), (0.07±0.09) and (0.41±0.15)LogMAR in the RCRT<35% group, RCRT≥35% group, RCRTing<69% group and RCRTing≥69% group, respectively.Significant differences were found in ABCVA between the RCRT<35% group and RCRT≥35% group (t=-6.27, -8.65, both at P<0.05). RCRT and RCRTing showed the positive correlations with ABCVA in the CSDME patients (r=0.86, 0.79, P<0.05). Conclusions RCRT and RCRTing can identify well the optimal responders to intravitreal ranibizumab and predict BCVA improvement after treatment.RCRT has better association with ABCVA than RCRTing.RCRTing may be preferable when retinal thickening is more severe. Key words: Diabetes retinopathy/drug therapy; Macular edema/therapy; Central retinal thickness; Vision; Antibodies, monoclonal, humanized; Tomography, optical coherence; Vitreous body

Evaluation of the Posterior Hyaloid Changes Following Intravitreal Injection of Ranibizumab for Diabetic Macular Edema

Purpose The aim of this work was to evaluate the posterior hyaloid changes and the effect on the vitreomacular relationship following intravitreal injection of ranibizumab (lucentis) for DME in diabetic patients attending the outpatient clinic of the Ophthalmology Department in Alexandria Main University Hospital. Patients and methods The study included 40 eyes. All of them received a baseline injection of 0.5 mg of intravitreal ranibizumab under sterile conditions. The injection was performed under topical anesthesia, with or without sedation. Further injections were administered Pro Re Nata (PRN ‘as required’) as decided in each subsequent follow-up visit if central retinal thickness remained 300 μm or greater or if there was a decrease in best-corrected visual acuity due to DME progression, confirmed with clinical evaluation and/or optical coherence tomography or other anatomic and clinical assessments. Results There were 12 male (54.2%) and 10 female patients (45.5%) between 45 and 71 years of age, with a mean value of 63.2 ± 12.6. There were five patients (22.7%) with type I and 17 patients (77.3%) with type II DM. The duration of DM was less than 10 years in six patients (27.3%) and more than 10 years in 16 patients (72.7%); it ranged between 9.5 and 20 years, with a mean value of 15.11 ± 7.98 years. HbA1c ranged from 7.11 to 8.25, with a mean value of 7.72 ± 0.892, and baseline visual acuity (TTDRS) ranged from 7.11 to 8.25, with a mean value of 53.13 ± 12.22. Baseline central macular thickness ranged from 301.0 to 525.0, with a mean value of 413.0 ± 107.0. No vitreous separation (category 1) was observed in 19 cases (47.5%), partial vitreomacular separation (VMS) (category 2) was observed in 12 cases (30%), vitreofoveal attachment with no traction (category 3) in seven cases (17.5%), and finally vitreofoveal attachment with traction (dome-shaped profile) (category 4) was observed in two cases (5%). No changes in vitreomacular relationship was seen in 16 cases (40%), partial VMS was seen in six cases (15%), vitreofoveal attachment with no traction was seen in eight cases (20%), vitreofoveal attachment with traction (dome-shaped profile) in three cases (7.5%), and complete VMS was seen in seven cases (17.5%). There was a statistically significant difference with regard to number of changes in VMR, partial VMS, vitreofoveal attachment with no traction, and vitreofoveal attachment with traction (dome-shaped profile). There was a statistically significant difference with regard to partial VMS, vitreofoveal attachment with no traction, and vitreofoveal attachment with traction (dome-shaped profile). There was a statistically significant relation between the number of injections and the outcome; the higher the number of injections, the better is the outcome.

The role of Anti‐VEGFs in the management of DME in vitrectomized eyes

SummaryThe role of Anti‐VEGFs in the management of diabetic macula edema (DME) is well established in large, randomized, controlled studies in eyes with naïve vitreous. The effect of Anti‐VEGFs may be altered in vitrectomized eyes and the question arises whether there is a difference in the efficacy of Anti‐VEGFs after vitrectomy. The replacement of the vitreous gel facilitates oxygen transport to the retina, as well as clearance of VEGF, thus VEGF and Anti‐VEGF pharmacokinetics can be altered. Pharmacokinetic data are largely based on experimental animal models but there is also a clinical impression that vitrectomized eyes have augmented pharmacokinetics with a faster clearance of Anti‐VEGFs and therefore their treatment could be less effective and requiring shorter treatment intervals, compared to non‐vitrectomized eyes. According to a study presented January 2015, vitrectomized eyes fared as well as non.vitrectomized eyes after treatment with ranibizumab for diabetic macular edema.

Efficacy and safety of ranibizumab in diabetic macular edema: real life study

PurposeTo evaluate the efficacy and safety of ranibizumabin patients with vision loss secondary to diabetic macular edema (DME).MethodsRetrospective analysis of a cohort of patients withvision loss (VA) due to DME and treated by ranibizumab. Patients were examined before treatment and during treatment every 4–6 weeks. Ophthalmologic examination included:measure of the best corrected visual acuity (BCVA) on the ETDRS scale, examination at the slit lamp, fundus, and SD‐OCT (Cirrus 5000, Carl Zeiss Meditec). All patients receiveda loading dose of 3 monthly injections followedby re‐treatments on an as‐needed basis (PRN regimen) The primary endpoint was the change in visual acuity at 12 months. The other criteria assessed were central retinal thickness (CRT) after loading dose, and at 12 months, and the number ofintravitreal injections (IVT) during the first year of follow‐up.Results109 eyes of 79 consecutive patients treateded since November 2012 have been included. At baseline the mean BCVA was 48.77 letters, the CRT was 517 microns. At 12 months the average BCVA was of 60.80 letters (p &lt; 0.05), with an average VA gain of +14.67 letters and 25% of patients had a BCVA&gt; 70 letters. The mean CRT after 3 injections was 344.32 microns (p &lt; 0.05) and 332 microns (p &lt; 0.05) at 12 months, with 57.23% of patients with CRT ≤ 300 microns. At 12 months the average VA in patients with CRT ≤ 300 microns was 63.51 letters (p &lt; 0.05) and the average AV in patients with ERC&gt; 300 .microns was 57.39 letters (p &lt; 0.05). The average number of IVT performed during the first year of follow up was 5.59. No serious adverse event was noted.ConclusionsPivotal studies have clearly shown the benefit of ranibizumab treatment of vision loss due to DME. This study in a “real life” setting confirms the results obtained in randomized trials.

Switching to ranibizumab for diabetic macular edema with persistent fluid on bevacizumab: Who is likely to benefit from the switch?

PurposeTo evaluate the efficacy of switching from bevacizumab to ranibizumab in patients with diabetic macular edema (DME).MethodsThe medical records of 41 DME eyes which showed persistent fluid after at least three monthly bevacizumab injections, and switched to ranibizumab injection were reviewed. Each patient received a single ranibizumab injection and followed up at 1 month. Anatomic responders to ranibizumab were followed up monthly and given ranibizumab injections on an as‐needed basis until 3 months.ResultsAt 1 month, the mean central foveal thickness (CFT) decreased from 431 μm to 349 μm (P &lt; .001), and mean best‐corrected visual acuity (BCVA) improved from 20/53 to 20/48 (P = .062). Twenty‐six eyes (65.9%) were classified as anatomical responders, and the mean CFT improved and maintained until 3 months (439 μm to 320 μm, P &lt; .001) after repeated injections (mean number: 2.8), while the mean BCVA stabilized (20/59 to 20/54, P = .075) in these eyes. Dry macula were achieved in 9 of 26 eyes at least once during the follow‐up period. Favorable anatomic response to ranibizumab at month 1 was related with previous partial response to bevacizumab.ConclusionsSwitching to ranibizumab may present an alternative option in the treatment of DME with persistent fluid after repeated bevacizumab injections, and the switch was more effective in eyes that showed partial response to previous bevacizumab.