Ensayos clínicos en el tratamiento del edema macular diabético

Diabetic macular edema (DME) is the main cause of visual acuity impairment in diabetic patients. The current standard therapy for patients with DME (focal/grid laser photocoagulation) usually does not improve impaired vision, and many patients continue to lose vision despite laser therapy. Vascular endothelial growth factor (VEGF) plays a key role in the pathogenesis of DME and is a major candidate as a therapeutic target for the treatment of DME. The advent of intravitreal anti-VEGF drugs, such a ranibizumab, has opened up a new era for the management of DME. The aim of this review is to summarize the evidence supporting the use of ranibizumab in clinical practice. The studies analyzed in this review are prospective, controlled, randomized clinical trials (RCT) that have focused on documenting the therapeutic effect of ranibizumab and its safety, providing encouraging results.     

Evidence-Based Treatment of Diabetic Macular Edema

ABSTRACT

Diabetes mellitus is a chronic disease that affects 415 million people worldwide. Despite treatment advances, diabetic eye disease remains a leading cause of vision loss worldwide. Diabetic macular edema (DME) is a common cause of vision loss in diabetic patients. The pathophysiology is complex and involves multiple pathways that ultimately lead to central retinal thickening and, if untreated, visual loss. First-line treatment of DME has evolved from focal/grid laser established by the Early Treatment of Diabetic Retinopathy Study (ETDRS) to intravitreous pharmacologic therapy. Landmark prospective clinical trials examining the effect of intravitreous injections of vascular endothelial growth factor (VEGF) inhibitors in the treatment of DME have demonstrated improved visual outcomes over focal grid laser. This review focuses on the scientific evidence treatment of DME, disease pathophysiology, clinical disease course, current treatment standards, and emerging novel therapeutic approaches.     

Diabetic macular oedema and visual loss: relationship to location,severity and duration

Purpose: To assess the relationship between visual acuity (VA) and diabetic macular oedema (DMO) in relation to the location of retinal thickening and the severity and duration of central macular thickening. Methods: Data from 584 eyes in 340 placebo‐treated patients in the 3‐years‐long Protein Kinase C Diabetic Retinopathy Study (PKC‐DRS2) trial were used to investigate the relationship between VA and DMO. Eligible eyes had moderately severe to very severe non‐proliferative diabetic retinopathy and VA of at least 45 letters on Early Treatment Diabetic Retinopathy Study (ETDRS) charts (Snellen equivalent = 20/125). Diabetic retinopathy and DMO status were assessed using stereo photographs. Results: Nearly one third of study eyes had foveal centre‐involving DMO at the start of the trial. Sustained moderate visual loss was found in 36 eyes, most commonly associated with DMO at the centre of the fovea in 73% of eyes. There was a strong relationship (p < 0.001) between foveal centre involvement with DMO and mean VA. Mean VA decreased with increasing retinal thickness at the centre (p < 0.001) and increasing duration of centre‐involving DMO (p < 0.001). Conclusion: This study documents the relationship between duration of DMO and progressive vision loss, and the key role of central foveal involvement in patients with diabetic retinopathy. These data will help to develop future strategies to prevent vision loss.     

Diabetic macular oedema: pilot randomised trial of pars plana vitrectomy vs macular argon photocoagulation

INTRODUCTION: Focal macular photocoagulation for clinically significant macular oedema (CSME) is the proven method for treatment of this condition, but with little chance of visual improvement. Pars plana vitrectomy (PPV) may produce resolution of macular oedema and improvement in visual acuity. However, there have been no randomised trials to ascertain role of vitrectomy in the management of persistent CSME. METHODS: Patients with persistent CSME despite previous macular photocoagulation and Snellen visual acuity 6/15 to 6/60 were recruited. Dilated fundoscopy, best-corrected visual acuity including Early Treatment Diabetic Retinopathy Study (ETDRS) vision, ocular coherence tomography and fundus fluorescein angiography (FFA) at baseline and up to 12 months post-treatment was performed. Exclusion criteria were signs of posterior vitreous detachment, macular traction or the taut posterior hyaloid face syndrome, or macular ischaemia on FFA. In all, 20 patients were randomised (10 in each arm) to either standard macular photocoagulation or PPV and removal of the posterior hyaloid face. RESULTS: Of the 20 patients recruited, seven patients completed the protocol in the vitrectomy and eight in the laser arms, respectively. There was little evidence of any difference in the foveal thickness at 12 months between the two treatment arms despite a gradual improvement. Only one patient, from the vitrectomy arm, suffered moderate visual loss (defined as loss of 15 ETDRS letters) (our primary outcome). DISCUSSION: In this pilot RCT, standard PPV provides little visual benefit compared to macular photocoagulation, but a larger definitive study is required to confirm this early appraisal.     

Ranibizumab for treatment of exudative age-related macular degeneration--own experience

It is commonly agreed nowadays that one of the key elements of neovascular age-related macular degeneration (AMO) pathogenesis is deregulation of the angiogenesis factors. Treatment of subfoveal choroidal neovascularizations (CNV) in course of AMD was limited to photodynamic therapy with verteporfin (PDT). The new approach to CNV treatment is to discover and eliminate factors, which directly induce CNV development. Extended studies have allowed to employ inhibitors of vascular endothelial growth factor (VEGF) for a treatment of neovascular AMD. Numerous of anti-VEGF compounds are still under developing in pre-clinical or phase-1/2 clinical studies whereas 2 of them have completed phase 3 of clinical trials. The newest compound that was launched on drug market is ranibizumab (Lucentis). Ranibizumab is a recombinant humanized IgG1 isotype, monoclonal antibody fragment designed for intravitreal use. Ranibizumab binds to and inhibits the biologic activity of human vascular endothelial growth factor A (VEGF-A). It has been proved on the base of MARINA and ANCHOR clinical trials that treatment ranibizumab is effective and save for patients treated for CNV secondary to AMD. PURPOSE: Interventional case series. MATERIAL AND METHODS: 67 eyes of 67 patients with all angiographic subtypes of wet AMD were treated with 0.5 mg of intravitreal ranibizumab, injected monthly for first 3 doses. Next doses were injected according to specified re-treatment criteria as assessed in monthly follow-up. RESULTS: Mean change in visual acuity (VA) was +12.4 ETDRS letters. Percent of patient losing less than 15 ETDRS letters was 93.2%. Percent of patient gaining VA more than 3 ETDRS letters was 43.4%. CONCLUSIONS: Intravitreal ranibizumab is effective in treatment of CNV due to AMD. A significant number of patients have improved theirs VA. Implementation of anti-VEGF therapy for treatment of ocular diseases gave a new hope for patient that previously couldn't be treated with any of method.     

Prevalence and incidence of blindness and other degrees of sight impairment in patients treated for neovascular age-related macular degeneration in a well-defined region of the United Kingdom

Aims

This study aimed to evaluate the incidence and prevalence of blindness, sight impairment, and other visual acuity (VA) states in patients receiving ranibizumab for neovascular age-related macular degeneration (nAMD) in Gloucestershire.

Methods

Serial VA and injection data for all treatment-naive patients receiving their first intravitreal injections of ranibizumab for nAMD in the Gloucestershire National Health Service Ophthalmology department between 2008 and 2010 were extracted from an electronic medical record system.

Results

The prevalence of blindness (VA in the better-seeing eye ≤25 Early Treatment Diabetic Retinopathy Study (ETDRS) letters) at the time of first intravitreal injection was 0.8%, increasing to 3.5% after 3 years. The prevalence of sight impairment (VA in the better-seeing eye 26–39 ETDRS letters) increased from 4.1% at baseline to 5.5% after 3 years. The incidence of initiating ranibizumab treatment for nAMD in people aged ≥50 years in Gloucestershire was 111 people per 100 000 population in 2009, and 97 people in 2010. The incidence of patients meeting the visual criteria for blindness and sight impairment registration from treated nAMD in people aged ≥50 years in Gloucestershire was 3.5 and 9.7 people, respectively per 100 000 population in 2010.

Conclusion

This is the first real-world study on the incidence and prevalence of eligibility for blindness and sight impairment registration in treated nAMD in the UK based on VA data. The incidence and prevalence of eligibility for certification of blindness or sight impairment in patients treated with ranibizumab for nAMD is low in Gloucestershire, with only 3.6% of the incident population progressing to blindness in 2010.     

Effect of laser photocoagulation treatment for diabetic macular oedema on patient's vision-related quality of life

PURPOSE: To evaluate the effect of laser photocoagulation for diabetic macular oedema (DME) on patients' Vision Related Quality Of Life (VR-QOL) and to investigate associations between changes in self reported VR-QOL and changes in visual acuity following application of laser treatment. METHODS: Prospective cohort study of 55 subjects who underwent laser treatment for DME. Eligible patients with no history of previous laser photocoagulation self-administered the 51-item field-test version of the National Eye Institute Visual Function Questionnaire (NEI-VFQ) prior to treatment and 3 months following the last session of laser application. Visual acuity was measured by means of the Early Treatment of Diabetic Retinopathy (ETDRS) chart. Multi-item scales rating different aspects of VR-QOL were compared prior and after photocoagulation and the change in questionnaire's composite score following treatment was correlated to change in visual acuity and other determinants previously reported as risk factors in the diabetic population. RESULTS: Scale scores associated with general vision, near vision, distance vision, peripheral vision, vision-specific social functioning, vision-specific mental health, expectations for visual function and dependency due to vision were significantly improved following laser treatment. Multivariate models revealed that improvement of the NEI-VFQ composite score was significant in subjects younger than 65 years of age (p = 0.04) who received more laser burns (p = 0.02) and had worse vision-related QOL prior to laser treatment as expressed by the baseline NEI- VFQ composite score (p = 0.03). There was no statistically significant association between change in the composite score following laser treatment and stage of diabetic retinopathy, duration of diabetes or laser settings used during photocoagulation. CONCLUSIONS: Photocoagulation for DME has a beneficial effect on patients' subjective perception of visual function. The use of vision-targeted health status questionnaires in conjunction with the clinical examination appears to provide a more comprehensive overview of individuals' daily well- being following laser treatment.     

Predictive factors for short-term visual outcome after intravitreal triamcinolone acetonide injection for diabetic macular oedema: an optical coherence tomography study

AIM: To evaluate the predictive factors for visual outcome after intravitreal triamcinolone acetonide injection to treat refractory diabetic macular oedema (DME). METHODS: A retrospective chart review of patients with DME who met the following inclusion criteria was performed: clinically significant diabetic macular oedema, receipt of a 4 mg/0.1 ml intravitreal triamcinolone acetonide injection and an optical coherence tomography (OCT) of the macula performed up to 10 days before injection. All patients received a full ophthalmic examination including best-corrected Snellen visual acuity (VA). The main outcome measure was the mean change in vision 3 months after injection. RESULTS: Data from 73 eyes of 59 patients were analysed. After a mean follow-up of 324 days, the mean change in vision was -0.075 logarithm of minimum angle of resolution (logMAR) units, with 27.3% improving > or =3 lines, 6.8% declining > or =3 lines and 60.2% remaining stable within 1 line of baseline vision. Statistical analysis was performed using multivariate generalised estimating equations on the basis of data from 52 eyes of 42 patients. Factors associated with an improvement in vision 3 months after injection were worse baseline VA (-0.27 logMAR units/unit increase in baseline VA, p = 0.002) and presence of subretinal fluid (-0.17 logMAR units, p = 0.06). The presence of cystoid macular oedema negatively affected the visual outcome (0.15 logMAR units, p = 0.03). In addition, the presence of an epiretinal membrane (ERM) was associated with less visual improvement. ERM modified the effect of baseline VA as demonstrated by a significant interaction between these two variables (0.34 logMAR units/unit increase in baseline VA, p = 0.04). CONCLUSIONS: OCT factors and baseline VA can be useful in predicting the outcomes of VA 3 months after intravitreal triamcinolone acetonide injection in patients with refractory DME.     

De la evidencia científica a la práctica clínica: pautas de tratamiento del edema macular diabético

Diabetic macular edema (DME) is now considered the leading cause of moderate vision loss in type 2 diabetic patients and has a high socioeconomic burden. In recent years, the therapeutic approach to this entity has changed. The role of laser treatment, considered the gold standard in clinical practice worldwide for more than 25 years, has been redefined. To understand current treatment algorithms, the pathophysiology of diabetic macular edema and the role played by vascular endothelial growth factor must be elucidated. Many clinical trials have emerged showing that intravitreal ranibizumab provides effective therapy with an acceptable safety profile. Based in these data, the European Medicines Agency has approved ranibizumab for the treatment of diabetic macular edema. This article aims to discuss new treatment options and the recently developed evidence-based algorithms.     

Intravitreal triamcinolone acetonide as an adjuvant therapy to panretinal photocoagulation for proliferative retinopathy with high risk characteristics in type 1 diabetes: case report with 22 weeks follow-up

PURPOSE: To describe a new treatment protocol to deliver panretinal photocoagulation that may avoid further deterioration of vision in patients with type 1 diabetes mellitus with proliferative retinopathy with high risk characteristics for severe visual loss and cystoid macular oedema. METHODS: Fundus photography, measurement of foveal thickness with optical coherence tomography and best corrected visual acuity (BCVA) determined by Snellen and ETDRS charts were measured before and after treatment in a 28-year-old man. RESULTS: Over 9 weeks, BCVA improved from 0.05 to 0.25 and the number of letters read at 2 metres from four to 39 after panretinal photocoagulation and adjuvant intravitreal triamcinolone injection under intraconal anaesthesia. Foveal thickness decreased from 691 microm to 239 microm and cysts disappeared by 15 weeks. By 22 weeks, foveal thickness had increased to 282 microm and small cysts had reappeared, but BCVA remained at 0.2 and the number of letters read at 30. CONCLUSION: Proliferative retinopathy regressed, cystoid macular oedema disappeared and vision improved after panretinal photocoagulation and adjuvant intravitreal triamcinolone acetonide injection under intraconal anaesthesia. This represents a feasible option in cases where pain during laser treatment and impairment of vision afterwards due to cystoid macular oedema result in poor compliance with standard laser treatment under topical anaesthesia.     

An efficacy comparison of anti-vascular growth factor agents and laser photocoagulation in diabetic macular edema: a network meta-analysis incorporating individual patient-level data

Background

This was an updated network meta-analysis (NMA) of anti-vascular endothelial growth factor (VEGF) agents and laser photocoagulation in patients with diabetic macular edema (DME). Unlike previous NMA that used meta-regression to account for potential confounding by systematic variation in treatment effect modifiers across studies, this update incorporated individual patient-level data (IPD) regression to provide more robust adjustment.

Methods

An updated review was conducted to identify randomised controlled trials for inclusion in a Bayesian NMA. The network included intravitreal aflibercept (IVT-AFL) 2?mg bimonthly (2q8) after 5 initial doses, ranibizumab 0.5?mg as-needed (PRN), ranibizumab 0.5?mg treat-and-extend (T&E), and laser photocoagulation. Outcomes included in the analysis were change in best-corrected visual acuity (BCVA), measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart, and patients with ≥10 and?≥?15 ETDRS letter gains/losses at 12?months. Analyses were performed using networks restricted to IPD-only and IPD and aggregate data with (i) no covariable adjustment, (ii) covariable adjustment for baseline BVCA assuming common interaction effects (against reference treatment), and (iii) covariable adjustments specific to each treatment comparison (restricted to IPD-only network).

Results

Thirteen trials were included in the analysis. IVT-AFL 2q8 was superior to laser in all analyses. IVT-AFL 2q8 showed strong evidence of superiority (95% credible interval [CrI] did not cross null) versus ranibizumab 0.5?mg PRN for mean change in BCVA (mean difference 5.20, 95% CrI 1.90–8.52 ETDRS letters), ≥15 ETDRS letter gain (odds ratio [OR] 2.30, 95% CrI 1.12–4.20), and ≥10 ETDRS letter loss (OR 0.25, 95% CrI 0.05–0.74) (IPD and aggregate random-effects model with baseline BCVA adjustment). IVT-AFL 2q8 was not superior to ranibizumab 0.5?mg?T&E for mean change in BCVA (mean difference 5.15, 95% CrI -0.26–10.61 ETDRS letters) (IPD and aggregate random-effects model).

Conclusions

This NMA, which incorporated IPD to improve analytic robustness, showed evidence of superiority of IVT-AFL 2q8 to laser and ranibizumab 0.5?mg PRN. These results were irrespective of adjustment for baseline BCVA.

     

Long-term effects of ranibizumab treatment delay in neovascular age-related macular degeneration

Background

Intravitreal injections of ranibizumab are the standard of care for neovascular age-related macular degeneration (AMD). In clinical trials, comparable efficacy has been shown for either monthly injections or as needed injections upon monthly controls. Unlike in trial settings, treatment in clinical routine is often delayed by complex approval procedures of health insurance and limited short-term surgical capacities.

Methods

Eighty-nine patients with neovascular AMD were followed for 12 months. Early treatment diabetic retinopathy study (ETDRS) visual acuity (VA), Radner reading VA and spectral domain optical coherence tomography were performed monthly, with additional fluorescein angiography if needed. After an initial loading phase of three consecutive monthly intravitreal injections with ranibizumab, re-injections were performed when recurrent activity of choroidal neovascularization (CNV) was detected.

Results

After an initial increase to a value of +5.0?±?11.87 ETDRS letters from baseline, VA constantly decreased over 12 months to a value of ?0.66?±?16.82 ETDRS letters below baseline. Central retinal thickness (CRT) decreased from a value of 438.1?±?191.4 μm at baseline to a value of 289.9?±?138.6 μm after initial therapy and stabilized at a value of 322.4?±?199.5 μm. Loss of VA during latency between indication to treat and treatment was significantly greater than re-gain of VA after re-initiation of therapy (?2.2?±?5.0 versus 0.4?±?7.4 letters; p?=?0.046).

Conclusions

Latency between indication to treat and treatment is responsible for irreversible VA deterioration. A successful PRN treatment regimen for neovascular AMD requires immediate access to therapy after indication.     

The RELATION study: efficacy and safety of ranibizumab combined with laser photocoagulation treatment versus laser monotherapy in NPDR and PDR patients with diabetic macular oedema

Purpose

To assess efficacy and safety of intravitreal ranibizumab 0.5 mg plus laser (COMBI) versus laser monotherapy (LASER) in patients with visual impairment due to diabetic macular oedema (DME) in either nonproliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR) and to analyse the relevance of inner versus outer retinal thickness.

Methods

In this double‐masked, multicentre phase IIIb study, patients (N = 128) were randomized (2:1) to receive COMBI (n = 85) versus LASER (n = 43). Patients received four initial monthly injections of ranibizumab 0.5 mg (COMBI) or sham (LASER) followed by pro re nata (PRN) injections. In both groups, patients received laser at baseline and additional laser at 3 monthly intervals, as needed. The study was started in 2010 and was prematurely terminated due to approval of ranibizumab for DME.

Results

The least squares (LS) mean change in mean best‐corrected visual acuity (BCVA) from baseline to month 12 was higher in the COMBI (6.5) versus LASER (2.3) group (LS mean difference: 4.2 [95% CI 0.9; 7.4] letters, p = 0.01, primary end‐point). There was also a tendency in the same direction for the subgroup of 26 patients with PDR (LS mean difference 14.7, p = 0.11). Mean central retinal thickness decreased by 107.3 μm in the COMBI group and by 80.3 μm in the LASER group from baseline to month 12 (p = 0.28). Ranibizumab was well tolerated.

Conclusion

This study showed that ranibizumab plus laser is a valuable treatment option for the management of DME. Patients with DME in PDR might also benefit from combined therapy compared to laser alone.     

Management of diabetic macular edema in Japan: a review and expert opinion

Diabetic retinopathy is a frequent cause of visual impairment in working-age adults (≥ 30 years) and in Japan is most commonly observed in those aged 50–69 years. Diabetic macular edema (DME) is one of the main causes of vision disturbance in diabetic retinopathy, which is a clinically significant microvascular complication of diabetes. Anti-vascular endothelial growth factor (VEGF) therapy is becoming the mainstay of treatment for DME. However, to achieve sustained long-term improvement in visual acuity, conventional laser photocoagulation, vitrectomy and steroid therapy are also expected to play a role in the treatment of DME. This review summarizes the epidemiology and pathology of diabetic retinopathy and DME, evaluates the findings regarding the diagnosis and treatment of DME, and underscores the importance of systemic management of the disease in the context of the current health care situation in Japan. Finally, the unmet needs of patients with DME and prospects for research are discussed. The weight of evidence suggests that it is important to establish a multipronged treatment strategy centered on anti-VEGF therapy.     

Pegaptanib sodium in treatment of choroidal neovascularization secondary to age-related macular degeneration. One year results

PURPOSE: Prospective, noncomparative (nonrandomized, uncontrolled), consecutive interventional case series study--to evaluate the efficacy of intravitreal pegaptanib sodium in the treatment of choroidal neovascularization due to age-related macular degeneration in treatment-naive patients. MATERIAL AND METHODS: 38 eyes of 38 patients were treated with intravitreal pegaptanib. All angiographic subtypes of lesions were qualified to the treatment. Intravitreal injections were performed every 6 weeks at the discretion of the treating ophthalmologist. Retreatment criteria were based on evaluation of presence of submacular fluid and/or increase in macular thickness seen in OCT, new retinal hemorrhage, and loss of visual acuity (VA). RESULTS: The VA outcomes were assessed at 48-th week of the study. The mean change in VA for all lesions was a loss of 9.4 ETDRS letters. Percent of patients losing less than 15 ETDRS letters in predominantly classic subgroup was 68%, minimally classic--65% and pure occult--72%. 7% of patients gained more than 1 ETDRS lines of VA whereas 2% more than 3 ETDRS lines. 8.5% of patients lost 30 and more ETDRS letters at 48-th week of the study. Results were better for smaller (<4 DA) lesions, eyes with better (> 54 ETDRS letters) baseline VA and for pure occult lesions. CONCLUSIONS: Pegaptanib sodium effectively preserve vision in approximately 70% of patients with wet AMD in 1-year period of observation. Eyes with more advanced lesions seen at baseline have an increased risk of worse VA outcomes.     

New developments in the pharmacological treatment of macular oedema due to retinal vein occlusion

The therapeutic options for retinal vascular diseases have changed due to new study results and the approval of dexamethasone (Ozurdex?) and ranibizumab (Lucentis?) by the EU commission for visual loss caused by macular oedema in retinal vein occlusion. In addition to laser treatment, we have now two approved drugs for the treatment of macular oedema. Therefore it is important to make decisions about the best treatment in retinal vein occlusion. This necessitates knowledge of the posology of the drug and assessment of the advantages and risks of the different treatment modalities. Therefore it is important to know the efficacy and safety data of the different therapies. The approval of dexamethasone and ranibicumab for the treatment of macular oedema in branch and central retinal vein occlusions improves the chances for the outcome, especially concerning visual acuity. The new results from the dexamethasone and ranibizumab studies in matters of efficacy and safety and treatment recommendations are described.     

Ranibizumab bei diabetischem Makulaödem

Background

Intravitreal anti-VEGF (vascular endothelial growth factor) therapy with ranibizumab has been shown to be an effective therapeutic option for foveal diabetic macular edema (DME). This prospective study evaluated the functional and morphological retinal changes after intravitreal ranibizumab treatment.

Material and methods

A consecutive prospective series of DME patients treated with intravitreal ranibizumab were examined before and after 3 and 6 months of intravitreal ranibizumab therapy. Best-corrected visual acuity (BCVA) according to the ETDRS protocol, retinal thickness in the macular area and central retinal thickness (CRT) measured with spectral-domain optical coherence tomography (SD-OCT) was determined. In addition, microperimetric functional macular mapping was determined before therapy and 4 weeks after the third injection.

Results

A total of 41 eyes from 33 patients were evaluated. During the 6-month observational period patients received a mean number of 5.2 injections. The mean BCVA increased significantly from 26?±?14 to 33?±?13 letters 4 weeks after the third injection and to 34?±?14 letters 6 months after starting the treatment. The mean CRT decreased significantly from 509?±?147 µm to 385?±?121 µm after the third injection and to 383?±?110 µm after 6 months. After 3 injections, the thickness of the most prominent central retinal area was less than 445 µm in 68.3% of patients and after a further 3 months of treatment in 78.0%.

Conclusion

The presented data demonstrate that intravitreal ranibizumab is effective for DME in everyday clinical practice and results are comparable to those of registration trials. After three initial injections significant structural and functional improvements were observed in a considerable number of patients.     

A grid pattern type of photocoagulation in treatment of diabetic maculopathy--personal experience

PURPOSE: The aim of the present study was the evaluation of visual outcome of 425 eyes in 283 patients treated by focal and grid pattern photocoagulation for clinically significant macular edema according to the recommendations of the Early Treatment Diabetic Retinopathy Study (ETDRS). MATERIAL AND METHODS: On the basis of baseline status of macula, eyes were classified into three groups: group I--eyes treated by focal photocoagulation (39 eyes), group II--eyes treated by focal photocoagulation and/or modified grid (84 eyes), group III--eyes treated by focal photocoagulation and/or grid pattern (302 eyes). Eligibility criteria for this retrospective study included a diagnosis of clinically significant macular edema according to the ETDRS scale. The baseline examination for all patients presented in this review included: the best corrected visual acuity (VA), slit lamp with contact lens indirect ophthalmoscopy, fundus color photography and fluorescein angiography. All patients were treated with argon green by grid with Nidek 2300 laser. Modified grid or focal photocoagulation according to the ETDRS recommendations were performed. Patients with proliferative diabetic retinopathy (PDR) were transferred to panretinal photocoagulation (PRP) after treatment of maculopathy. Development of VA from the baseline to last checkup in treated eyes was reported and compared. Follow-up ranged widely from 6 to 45 months. RESULTS: General stabilization was achieved in 51.3%, improvement in 10.1% and deterioration in 38.6% of eyes. The best results were achieved after selective and focal and/or modified grid treatment: in the Ist group stabilization of VA was achieved in 43.6% and improvement in 41% of eyes; in the IInd group: stabilization in 60.7% and improvement in 21.4% were stated; in the IIIrd group: stabilization in 49.7% and improvement only in 3.0%. In 164 (38.6%) cases supplemental treatment was administered. CONCLUSION: Photocoagulation has proved effective in the treatment of diabetic clinically significant macular edema.     

Review of Ranibizumab Trials for Neovascular Age-Related Macular Degeneration

Ranibizumab, a recombinant, humanized, monoclonal antibody antigen-binding fragment that neutralizes all VEGF-A isoforms, is the first US FDA-approved therapy for neovascular age-related macular degeneration (AMD) to result in improvement in visual acuity. The benefit of intravitreal ranibizumab applies to all angiographic subtypes of neovascular AMD and across all lesion sizes. The two original phase III studies (ANCHOR and MARINA) demonstrated sustained visual acuity (VA) gains over a two-year monthly dosing schedule. Following these trials, several studies looked at ways to decrease the treatment burden while maintaining similar visual gains. These trials included PIER, PrONTO, EXCITE, SUSTAIN, HORIZON, and CATT. Visual acuity data shows that monthly dosing of ranibizumab produces superior vision outcomes compared to a less-frequent, fixed-dosing schedule. Intravitreal ranibizumab is well tolerated and shown to have a very low rate of adverse ocular or systemic side-effects.     

Review of ranibizumab trials for neovascular age-related macular degeneration

Ranibizumab, a recombinant, humanized, monoclonal antibody antigen-binding fragment that neutralizes all VEGF-A isoforms, is the first US FDA-approved therapy for neovascular age-related macular degeneration (AMD) to result in improvement in visual acuity. The benefit of intravitreal ranibizumab applies to all angiographic subtypes of neovascular AMD and across all lesion sizes. The two original phase III studies (ANCHOR and MARINA) demonstrated sustained visual acuity (VA) gains over a two-year monthly dosing schedule. Following these trials, several studies looked at ways to decrease the treatment burden while maintaining similar visual gains. These trials included PIER, PrONTO, EXCITE, SUSTAIN, HORIZON, and CATT. Visual acuity data shows that monthly dosing of ranibizumab produces superior vision outcomes compared to a less-frequent, fixed-dosing schedule. Intravitreal ranibizumab is well tolerated and shown to have a very low rate of adverse ocular or systemic side-effects.