Laser Monotherapy Research Articles

Combination of Hydroquinone and Fractional CO2 Laser versus Hydroquinone Monotherapy in Melasma Treatment: A Randomized, Single-blinded, Split-face Clinical Trial.

Background:Melasma is a chronic hyperpigmentation skin disorder mainly affecting women in the reproductive age. Available treatments for melasma do not lead to long-term satisfactory results.Aims:This study aimed to compare the efficacy of fractional CO2 laser in combination with topical therapy to topical therapy alone.Materials and Methods:Forty women with bilateral melasma were studied in this randomized single-blinded clinical trial. Each side of the face was randomly allotted to either topical hydroquinone 4% or combination of topical hydroquinone 4% and fractional CO2 laser. Patients received three sessions of laser therapy at 3-week intervals. Hydroquinone 4% application on both sides maintained for 3 months after the last laser session. The clinical improvement (darkness [D] and homogeneity [H] of hyperpigmentation) was measured by a blinded main investigator and an outcome assessor. Furthermore, improvement was assessed by physician's global assessment (PGA) and patient satisfaction (visual analog scale [VAS] score).Results:Significant reduction in D observed 3 weeks after combination therapy (P<0.001) and 6 weeks after monotherapy (P<0.001). Reduction in H became significant after 6 weeks in both groups (P<0.001). However, the two methods were not considerably different in any session (P>0.05). Furthermore, control and experiment sides were not significantly different considering VAS score and PGA (P>0.05).Conclusion:Considering the short-term outcome of laser and hydroquinone therapy, we can apply it to obtain earlier positive results. However, because of the lack of significant difference between the two methods and also the high cost of laser therapy, it seems better not to recommend fractional CO2 laser to patients as adjunctive therapy for long-term treatment of melasma.

The effectiveness of topical therapy combined with 308-nm excimer laser on vitiligo compared to excimer laser monotherapy in pediatric patients.

We evaluated the efficiency of using a 308-nm excimer laser with either tacrolimus, pimecrolimus, or halometasone for the treatment of childhood vitiligo. Patients who received combined treatments had significantly higher rates of repigmentation in comparison with individuals who underwent excimer laser alone therapy. Moreover, patients who received treatment with excimer laser and halometasone had significantly higher rates of repigmentation, even higher than individuals who were treated with tacrolimus combined or pimecrolimus combined. This regimen was more effective on the face, neck, and limbs. We conclude that the use of a combined excimer laser and halometasone cream has a greater therapeutic effect than laser alone.

Association of Changes in Macular Perfusion With Ranibizumab Treatment for Diabetic Macular Edema

Anti-vascular endothelial growth factor treatment is the first-line therapy in the treatment of center-involving diabetic macular edema. Data on capillary perfusion changes under repeated treatment in a possibly compromised vascular network are limited. To evaluate the association of repeated ranibizumab injections on macular perfusion in patients with diabetic macular edema. This study analyzed prospectively collected data from the 12-month RESTORE core study and the 24-month open label RESTORE extension study, which assessed the efficacy and safety of ranibizumab in patients with visual impairment due to diabetic macular edema. Of 345 patients with center-involving diabetic macular edema who had enrolled in the 12-month RESTORE core study, 240 entered the 24-month RESTORE extension study. Of these, 83 (34.6%) received ranibizumab, 83 (34.6%) received ranibizumab and laser combination therapy, and 74 (30.8%) received laser monotherapy in the first year of the study; 208 completed the 24-month extension study. Fluorescence angiography images were taken from each participant twice each year graded by Vienna Reading Center on severity of capillary loss in the parafoveal area, regularity of the foveal avascular zone outline, and measurement of the size of the foveal avascular zone, following a standardized protocol. Data analysis took place from July 2014 through December 2017. Change in 3 fluorescence angiography perfusion parameters over the course of treatment. Mean (SD) patient age was 62.6 (8.8) years; 124 of 208 (59.2%) were male and 197 of 208 (94.6%) were white. The number of patients with definite altered foveal avascular zone regularity at baseline was 103 of 240 patients (42.9%); another 118 patients (49.2%) had questionably altered regularity at baseline. Definitive capillary loss was found in 65 of 240 patients (27.1%) at baseline. Mean (SD) foveal avascular zone size at baseline was 0.261 (0.232) mm2 in ranibizumab monotherapy, 0.231 (0.219) mm2 in ranibizumab and macular laser combination therapy, and 0.201 (0.13) mm2 in laser monotherapy. No treatment arm experienced significant increase in foveal avascular zone size at any time in the study period. At month 36, ranibizumab monotherapy resulted in a mean increase of 0.073 mm2 (95% CI, 0.005-0.142 mm2) and combination therapy resulted in a mean increase of 0.117 mm2 (95% CI, 0.045-0.188 mm2), but no changes were statistically significant. No changes occurred in foveal avascular zone regularity in any treatment group, and no differences were found in capillary loss around the fovea in the 3 treatment groups; neither element could be correlated with visual acuity or central retinal thickness. Repeated ranibizumab treatment was not associated with impaired macular perfusion in our study cohort. Because our data do not suggest a harmful effect of anti-vascular endothelial growth factor therapy on capillary integrity, patients with severe microangiopathy and advanced capillary dropout should not be denied these treatments.

Therapeutic efficacy and safety of a 1927-nm fractionated thulium laser on pattern hair loss: an evaluator-blinded, split-scalp study.

Laser- or light-assisted therapies have been used to improve the perifollicular environment by upregulating the expression of growth factors and signaling molecules for hair restoration. The aim of our study was to preclinically and clinically evaluate the therapeutic efficacy and safety of a 1927-nm fractionated thulium laser on pattern hair loss (PHL). An in vivo hairless mouse study and an in vivo human skin environmental scanning electron microscopy (ESEM) study were performed with different power and energy settings. Thereafter, an evaluator-blinded, split-scalp study was conducted to evaluate hair thickness and density in 10 PHL patients treated with 12 sessions of fractionated thulium laser treatment with or without post-laser treatment application of a growth factor-containing (GF) solution. In in vivo hairless mouse skin, inverted cone-shaped zones of thulium laser-induced tissue coagulation (LITC) were noted immediately after treatment in the epidermis and upper to mid-dermis without remarkable ablative tissue injury. The ESEM study revealed round to oval-shaped zones of non-ablative LITC on the surface of the stratum corneum of a human subject immediately after laser irradiation. In PHL patients, 12 sessions of thulium laser monotherapy at 1-week intervals resulted in significantly increased hair density and thickness. Post-laser treatment application of GF solution offered additional therapeutic efficacy by improving hair density and thickness on the split scalp. The use of a fractionated thulium laser with or without post-laser therapy application of GF solution to treat PHL elicited remarkable improvements in hair thickness and hair counts.

Low frequency ranibizumab versus dexamethasone implant for macular oedema secondary to branch retinal vein occlusion

BackgroundThe aim was to make a real‐world comparison of the efficacy of ranibizumab, dexamethasone and grid laser treatments in macular oedema due to branch retinal vein occlusion (BRVO).MethodsForty‐four eyes of 44 consecutive patients with macular oedema secondary to BRVO were included. Treatment arms comprised standard care (StCARE, n = 15), intravitreal ranibizumab (RNB, n = 14) and dexamethasone implant (DEX, n = 15). No rescue laser was performed in DEX and RNB groups. Main outcome measures were mean change in visual acuity (VA) and the percentage of patients who gained 10 or more letters from baseline to six months and central retinal thickness (CRT).ResultsImprovements in mean logMAR VA (p = 0.642) and letter score from baseline to month 6 were not statistically significantly different in all three groups. Mean follow‐up was 13.9 ± 10.7 months in RNB, 11.9 ± 6.3 in DEX and 11.4 ± 6.6 in StCARE. Mean number of injections was 2.4 ± 1.4 (range: 1–6) in RNB and 1.9 ± 0.7 (range: 1–3) in DEX group over the follow‐up period. Mean letter gain was 13.5 in DEX (p = 0.067), 7.1 in RNB (p = 0.553) and 4.5 in StCARE (p = 0.362). Mean CRT at baseline was 512.8 μm in DEX, 505.1 μm in RNB and 345.5 μm in the StCARE group. At the last visit, RNB provided the maximum reduction in CRT. Mean CRT decrease was −146.5 μm (28.6 per cent) in DEX, −241.3 μm (47.8 per cent) in RNB and −45.6 μm (13.2 per cent) in StCARE (p = 0.030). A statistically significant intraocular pressure elevation occurred in the DEX group (p = 0.005).ConclusionBoth RNB and DEX provided a significant resolution in macular oedema. Low frequency injections limited the visual gain in ranibizumab therapy. Visual results could be better with higher frequency injections and early start of treatment. Dexamethasone implants may be preferable in terms of visual improvement under low frequency injection conditions. Close follow‐up is mandatory for detection of intraocular pressure elevations. Laser monotherapy is not a reasonable first‐line option in the era of injection therapies.

Effect of laser therapy on quality of life in patients with radiation-induced breast telangiectasias.

To evaluate the effects of laser monotherapy on quality of life in breast cancer patients with chronic radiation dermatitis. A prospective, IRB-approved study was conducted at Memorial Sloan Kettering Cancer Center. Breast cancer patients with chronic radiation dermatitis completed health-related quality of life (HR-QOL) questionnaires before and after laser monotherapy for radiation-induced breast telangiectasias (RIBT). After informed consent, all patients were issued the Skindex-16 and Breast-Q Adverse Effects of Radiation HR-QOL questionnaires prior to receiving laser treatment. Patients were treated with a 595 nm pulsed dye laser at 4- to 6-week intervals, with percent telangiectasia clearance and adverse events recorded at each visit. Post-treatment HR-QOL questionnaires were collected after clinician-assessed telangiectasia clearance of >50%. Median HR-QOL scores before and after therapy were reported for individual HR-QOL domains (Skindex-16) and HR-QOL totals (Skindex-16 and Breast-Q Adverse Effects of Radiation). Before- and after-differences were calculated using the Wilcoxon Signed-Rank Test. Twenty-two female patients (average age 56 years) enrolled in this study. A majority (13/22, 59%) exhibited telangiectasias across the décolletage and axilla in addition to the breast. Sixteen patients reached the 50% RIBT clearance threshold during the study period, and 11 of these patients (69%) completed follow-up HR-QOL questionnaires. Patients showed statistically significant improvements in emotional and functional Skindex-16 HR-QOL domains and in overall Skindex-16 HR-QOL score. Breast-Q scores also improved significantly, illustrating a decrease in specific physical and cosmetic concerns common to radiated breast skin. Common adverse events were transient post-treatment pain and redness. Breast cancer patients with RIBT presented with substantial deficits in several HR-QOL arenas. Laser monotherapy effectively treated the appearance of radiation dermatitis in these patients and also significantly improved HR-QOL. Lasers Surg. Med. 50:284-290, 2018. © 2017 Wiley Periodicals, Inc.

Sustained Benefits of Ranibizumab with or without Laser in Branch Retinal Vein Occlusion: 24-Month Results of the BRIGHTER Study

To evaluate the long-term (24-month) efficacy and safety of ranibizumab 0.5 mg administered pro re nata (PRN) with or without laser using an individualized visual acuity (VA) stabilization criteria in patients with visual impairment due to macular edema secondary to branch retinal vein occlusion (BRVO). Phase IIIb, open-label, randomized, active-controlled, 3-arm, multicenter study. A total of 455 patients. Patients were randomized (2:2:1) to ranibizumab 0.5 mg (n= 183), ranibizumab 0.5 mg with laser (n= 180), or laser (with optional ranibizumab 0.5 mg after month 6; n= 92). After initial 3 monthly injections, patients in the ranibizumab with or without laser arms received VA stabilization criteria-driven PRN treatment. Patients assigned to the laser arm received laser at the investigator's discretion. Mean (and mean average) change in best-corrected visual acuity (BCVA) and central subfield thickness (CSFT) from baseline to month 24, and safety over 24 months. A total of 380 patients (83.5%) completed the study. Ranibizumab with or without laser led to superior BCVA outcomes versus laser (monotherapy and combined with ranibizumab from month 6; 17.3/15.5 vs. 11.6 letters; P < 0.0001). Ranibizumab with laser was noninferior to ranibizumab monotherapy (mean average BCVA change: 15.4 vs. 15.0 letters; P < 0.0001). However, addition of laser did not reduce the number of ranibizumab injections (mean injections: 11.4 vs. 11.3; P= 0.4259). A greater reduction in CSFT was seen with ranibizumab with or without laser versus laser monotherapy over 24 months from baseline (ranibizumab monotherapy-224.7 μm, ranibizumab with laser-248.9 μm, laser [monotherapy and combined with ranibizumab from month 6]-197.5 μm). Presence of macular ischemia did not affect BCVA outcome or treatment frequency. There were no reports of neovascular glaucoma or iris neovascularization. No new safety signals were identified. The BRIGHTER study results confirmed the long-term efficacy and safety profile of PRN dosing driven by individualized VA stabilization criteria using ranibizumab 0.5 mg in patients with BRVO. Addition of laser did not lead to better functional outcomes or lower treatment need. The safety results were consistent with the well-established safety profile of ranibizumab.

Efficiency and safety of laser photocoagulation with or without intravitreal ranibizumab for treatment of diabetic macular edema: a systematic review and Meta-analysis.

To compare the therapeutic effect and safety of laser photocoagulation along with intravitreal ranibizumab (IVR) versus laser therapy in treatment of diabetic macular edema (DME). Pertinent publications were identified through comprehensive searches of PubMed, EMBASE, Web of Science, Cochrane Library, and ClinicalTrials.gov to identify randomized clinical trials (RCTs) comparing IVR+laser to laser monotherapy in patients with DME. Therapeutic effect estimates were determined by weighted mean differences (WMD) of change from baseline in best corrected visual acuity (BCVA) and central retinal thickness (CRT) at 6, 12, or 24mo after initial treatment, and the risk ratios (RR) for the proportions of patients with at least 10 letters of improvement or reduction at 12mo. Data regarding major ocular and nonocular adverse events (AEs) were collected and analyzed. The Review Manager 5.3.5 was used. Six RCTs involving 2069 patients with DME were selected for this Meta-analysis. The results showed that IVR+laser significantly improved BCVA compared with laser at 6mo (WMD: 6.57; 95% CI: 4.37-8.77; P<0.00001), 12mo (WMD: 5.46; 95% CI: 4.35-6.58; P<0.00001), and 24mo (WMD: 3.42; 95% CI: 0.84-5.99; P=0.009) in patients with DME. IVR+laser was superior to laser in reducing CRT at 12mo from baseline with statistical significance (WMD: -63.46; 95% CI: -101.19 to -25.73; P=0.001). The pooled RR results showed that the proportions of patients with at least 10 letters of improvement or reduction were in favor of IVR+laser arms compared with laser (RR: 2.13; 95% CI: 1.77-2.57; P<0.00001 and RR: 0.37; 95% CI: 0.22-0.62; P=0.0002, respectively). As for AEs, the pooled results showed that a significantly higher proportion of patients suffering from conjunctival hemorrhage (study eye) and diabetic retinal edema (fellow eye) in IVR+laser group compared to laser group (RR: 3.29; 95% CI: 1.53-7.09; P=0.002 and RR: 3.02; 95% CI: 1.24-7.32; P=0.01, respectively). The incidence of other ocular and nonocular AEs considered in this Meta-analysis had no statistical difference between IVR+laser and laser alone. The results of our analysis show that IVR+laser has better availability in functional (improving BCVA) and anatomic (reducing CRT) outcomes than laser monotherapy for the treatment of DME. However, the patients who received the treatment of IVR+laser may get a higher risk of suffering from conjunctival hemorrhage (study eye) and diabetic retinal edema (fellow eye).

Comparison Study of Efficacyinvolving Intravitreal Ranibizumab Versus Standard Laser Mono Therapy in Patients with Visual Impairment Due To Diabetic Macula Edema

Comparison Study of Efficacyinvolving Intravitreal Ranibizumab Versus Standard Laser Mono Therapy in Patients with Visual Impairment Due To Diabetic Macula Edema

Polypoidal choroidal vasculopathy

The article presents literature review devoted to the issue of polypoidal choroidal vasculopathy. The studies of Russian and foreign researchers were reviewed. Epidemiological and clinical characteristics of polypoidal choroidal vasculopathy, diagnostic features and modern treatment methods, the results of clinical studies are presented. Polypoidal choroidal vasculopathy is a subtype of neoascular AMD with specific characteristics including predisposition of certain races, clinical features, serosanguineous complications of different severity, tendency to relapsing course of neovascularization and development of secondary serosanguineous exfoliation. It was registered most frequently in patients aged 50 to 65 years. Prevalence among Caucasians is 4 to 9.8%, and among Asians - 23.9 to 54.7%. Diagnosis of polypoidal choroidal vasculopathy requires the use of fluorescent angiography, indocyanine green angiography and optical coherence tomography. Polyps regression accordng to angiography is considered one of the aims of initial therapy of active polypoidal choroidal vasculopathy. According to Expert group of polypoidal choroidal vasculopathy, while using laser photocoagulation and photodynamic therapy, affecting both polyps and vasculature is required. As a result of the analysis of population studies, the results of treatment with laser coagulation, photodynamic therapy (independently and in combination with angiogenesis inhibitors) and monotherapy with angiogenesis inhibitors were demonstrated. Regardless of the achieved results of polypoidal choroidal vasculopathy diagnosis, the treatment issues require further investigation. Additional studies are required to evaluate long-term correlation between initial polyp regression, relapses, response to repeated therapy and functional results.

Laser treatment of onychomycosis due to Neoscytalidium dimidiatum: An open prospective study.

Conventional systemic and topical treatments have proven ineffective for the treatment of onychomycosis caused by Neoscytalidium dimidiatum. Our aim was to evaluate the effectiveness and safety of laser monotherapy for the treatment of onychomycosis caused by this pathogen. Patients with clinical onychomycosis of the toenails and positive results both on direct mycological examination and N. dimidiatum culture underwent four 1064nm Nd:YAG laser sessions with 6-week intervals between sessions. Participants were monitored by clinical examination supported by dermoscopy, measurement of diseased nail and the onychomycosis severity index (OSI), and by mycological examination for 12 months after completion of treatment. Treatment outcome was based on clinical and laboratory criteria and was divided in complete or partial cure, clinical improvement, treatment failure and relapse. No patient had complete or partial cure at any time during the study. Clinical improvement was observed in 40.6% of the patients at the end of the laser sessions; however, it did not persist during the follow-up. Treatment failure was observed in 64.7% of the patients at the end of 12 month follow-up period. Direct microscopy and culture results remained positive in most patients. Adverse events, in addition to treatment-related pain, were observed and considered severe in one case. The 1064 nm Nd:YAG laser was not able to cure onychomycosis caused by N. dimidiatum but temporarily improved the clinical appearance of the nail; however, adverse events may occur.

Laser and Anti-Vascular Endothelial Growth Factor Agent Treatments for Retinal Arterial Macroaneurysm.

To describe the efficacy of laser and intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents for patients with symptomatic retinal arterial macroaneurysm (RAM). From 2009 to 2016, we collected patients with exudative or hemorrhagic RAM all treated by focal laser photocoagulation. Nd:YAG laser was performed in patients with subinternal limiting membrane (sub-ILM) hemorrhage. Intravitreal anti-VEGF agents were given in eyes with macular exudation as adjuncts. Changes of visual acuity and central foveal thickness before and after treatment were recorded and compared with Wilcoxon signed-rank test. Thirty-five eyes that underwent a single session of laser photocoagulation for RAM resulted in macroaneurysm regression. The hemorrhagic group included 24 eyes having ruptured macroaneurysms without macular exudation. Five eyes with simultaneous sub-ILM hemorrhage receiving Nd:YAG laser membranotomy had resolution of preretinal hemorrhage. Exudative RAM having cystoid macular edema or submacular fluid with or without ruptured macroaneurysms was treated by focal laser photocoagulation alone in 3, or combined with single intravitreal anti-VEGF agent in 8 eyes. All patients had significantly improved vision when comparing visual acuity at baseline and final follow-up (P = 0.00016). Significant reduction of macular thickness was also observed after laser monotherapy or combined treatment in exudative RAM (P = 0.018). Focal laser photocoagulation was helpful for the management of ruptured or leaky RAM. Combined focal laser and intravitreal anti-VEGF agents could better reduce macular exudation caused by RAM. Additionally, Nd:YAG laser was a safe and effective method to remove the sub-ILM hemorrhage caused by RAM.

Refractive outcomes following the treatment of retinopathy of prematurity in the anti-VEGF era: a literature review

A growing body of evidence indicates that antivascular endothelial growth factor (VEGF) therapy is effective in the treatment of retinopathy of prematurity (ROP). We conducted a comprehensive literature review on refractive outcomes of anti-VEGF treatments compared to laser treatment or a combination of laser therapy and anti-VEGF injections. Of the 9 studies analyzed, the final mean refractive error was myopic in 3 studies (37%) with IVB monotherapy, 7 studies (87.5%) with laser photocoagulation, and 1 study (50%) with combined therapy. In comparing IVB with laser monotherapy, 6 of 7 studies (86%) reported that final refractive error was significantly more myopic (>1 D) after laser treatment. No study was graded as high quality, and only a single article provided moderate quality of evidence.

Bevacizumab Monotherapy or Combined with Laser versus Laser Monotherapy in Mongolian Patients with Diabetic Macular Edema

Objectives: To evaluate the efficacy and safety of bevacizumab monotherapy and bevacizumab therapy combined with laser therapy versus laser monotherapy in Mongolian patients with visual impairment due to diabetic macular edema (DME). Methods: One hundred twelve eligible patients, aged ^18 years, with type 1 or 2 diabetes mellitus and best corrected visual acuity (BCVA) in the study eye of 35 to 69 Early Treatment Diabetic Retinopathy Study letters at 4 m (Snellen equivalent: &gt;6/60 or &lt;6/12), and with visual impairment due to center-involved DME were included in the study. Patients were randomized into three treatment groups: (1) intravitreal bevacizumab monotherapy (n = 42), (2) intravitreal bevacizumab combined with laser therapy (n = 35), and (3) laser monotherapy (n = 35). Bevacizumab injections were given for three initial monthly doses and then pro re nata thereafter based on BCVA stability and DME progression. The primary efficacy endpoints were the mean change in BCVA and central retinal subfield thickness from baseline to month 12. Results: Bevacizumab monotherapy and bevacizumab + laser were superior to laser monotherapy in improving the mean change in BCVA letter score from baseline to month 12 (+8.3 and +11.3 vs +1.1 letters; both p &gt;&lt;0.0001). At month 12, a greater proportion of patients gained &gt;10 and &gt;15 letters and had a BCVA letter score &gt;73 (Snellen equivalent: &gt;6/12) with bevacizumab monotherapy (23.8% and 7.1% and 4.8%, respectively) and bevacizumab + laser (57.1% and 28.6% and 14.3%, respectively) versus laser monotherapy (0% and 0% and 0%, respectively). The mean central retinal subfield thickness was significantly reduced from baseline to month 12 with bevacizumab (-124.4 pm) and bevacizumab + laser (-129.0 pm) versus laser (-62.0 pm; both p = 0.002). Conjunctival hemorrhage was the most common ocular event. No endophthalmitis cases occurred. Conclusion: Bevacizumab monotherapy or bevacizumab + laser showed superior BCVA improvements over macular laser treatment alone in Mongolian patients with visual impairment due to DME.

Cost-effectiveness of ranibizumab in the treatment of visual impairment due to diabetic macular edema

Objective Ranibizumab, an anti-vascular endothelial growth factor designed for ocular use, has been deemed cost-effective in multiple indications by several Health Technology Assessment bodies. This study assessed the cost-effectiveness of ranibizumab monotherapy or combination therapy (ranibizumab plus laser photocoagulation) compared with laser monotherapy for the treatment of visual impairment due to diabetic macular edema (DME).Methods A Markov model was developed in which patients moved between health states defined by best-corrected visual acuity (BCVA) intervals and an absorbing ‘death’ state. The population of interest was patients with DME due to type 1 or type 2 diabetes mellitus. Baseline characteristics were based on those of participants in the RESTORE study. Main outputs were costs (in 2013 CA$) and health outcomes (in quality-adjusted life-years [QALYs]) and the incremental cost-effectiveness ratio (ICER) was calculated. This cost-utility analysis was conducted from healthcare system and societal perspectives in Quebec.Results From a healthcare system perspective, the ICERs for ranibizumab monotherapy and combination therapy vs laser monotherapy were CA$24 494 and CA$36 414 per QALY gained, respectively. The incremental costs per year without legal blindness for ranibizumab monotherapy and combination therapy vs laser monotherapy were CA$15 822 and CA$20 616, respectively. Based on the generally accepted Canadian ICER threshold of CA$50 000 per QALY gained, ranibizumab monotherapy and combination therapy were found to be cost-effective compared with laser monotherapy. From a societal perspective, ranibizumab monotherapy and combination therapy provided greater benefits at lower costs than laser monotherapy (ranibizumab therapy dominated laser therapy).Conclusions Ranibizumab monotherapy and combination therapy resulted in increased quality-adjusted survival and time without legal blindness and lower costs from a societal perspective compared with laser monotherapy.

PSS7 - Efficacy Comparison of Anti-Vegf and Laser Photocoagulation in the Treatment of Visual Impairment due to Diabetic Macular Edema: a Systematic Review and Network Meta-Analysis

Objective: Compare the efficacy of ranibizumab, aflibercept, laser, and sham in the first-line treatment of diabetic macular edema (DME) to inform technology assessments such as those conducted by the UK National Institute for Health and Care Excellence (NICE). Data sources: MEDLINE, Embase, Cochrane Library, congress abstracts, ClinicalTrials.gov registry and Novartis data on file. Inclusion criteria: Studies reporting 6- or 12-month results of randomized controlled trials (RCTs) evaluating at least two of ranibizumab 0.5 mg pro re nata, aflibercept 2.0 mg bi-monthly, laser photocoagulation or sham. Study quality was assessed based on likelihood of bias in selection, attrition, detection and performance. Outcome measure: Improvement in best-corrected visual acuity (BCVA) measured as the proportion of patients gaining $10 letters on the Early Treatment Diabetic Retinopathy Study scale. The outcome was chosen following acceptance by NICE of a Markov model with 10-letter health states in the assessment of ranibizumab for DME. Meta-analysis: Bayesian network meta-analyses with fixed and random effects adjusted for differences in baseline BCVA or central retinal thickness. Results: The analysis included 1,978 patients from eight RCTs. The random effects model adjusting for baseline BCVA was the best model based on total residual. The efficacy of ranibizumab was numerically, but not statistically, superior to aflibercept (odds ratio [OR] 1.59; 95% credible interval [CrI], 0.61–5.37). Ranibizumab and aflibercept were statistically superior to laser monotherapy with ORs of 5.50 (2.73–13.16) and 3.45 (1.62–6.84) respectively. The probability that ranibizumab is the most efficacious treatment was 73% compared with 14% for aflibercept, 12% for ranibizumab plus laser, and 0% for laser. Limitations: Three of the eight RCTs included are not yet published. The models did not adjust for all potential effect modifiers. Conclusion: Ranibizumab was non-significantly superior to aflibercept and both anti-VEGF therapies had statistically superior efficacy to laser.

Three-year patient-reported visual function outcomes in diabetic macular edema managed with ranibizumab: the RESTORE extension study

Objective:To determine the impact of ranibizumab 0.5 mg on patient-reported visual function over 36 months in individuals with visual impairment from diabetic macular edema.Methods:RESTORE comprises a phase 3, randomized, multicenter, 12 month core study and a 24 month open-label extension study. Eyes assigned to ranibizumab in the core study received ranibizumab for 36 months; eyes assigned to laser monotherapy in the core study received ranibizumab during the extension. The primary outcome was least-squares mean change in National Eye Institute 25-item Visual Functioning Questionnaire (NEI VFQ-25) overall composite and subscale scores.Results:Of 303 core study participants, 240 (79%) entered the extension, comprising 83 (35%) participants initially assigned to ranibizumab, 83 (35%) assigned to ranibizumab plus laser combination therapy, and 74 (31%) assigned to laser monotherapy. Least-squares mean (standard error) change in NEI VFQ-25 composite score from baseline to month 12 (+5.9 [1.5]; +5.0 [1.5], for the ranibizumab and combination therapy groups, respectively) decreased by month 36 (+4.1 [1.7]; +4.0 [1.7], respectively, from baseline to month 36) following reduced injection frequency relative to the core study. At 36 months, the least-squares mean (standard error) change in the laser monotherapy group was similar to that in the ranibizumab groups (+4.1 [1.8]). Most subscale scores showed outcomes similar to that for the composite score. The greatest NEI VFQ-25 gains were consistently observed in participants for whom the study eye was the better-seeing eye.Limitations:Patients entering the extension were not randomized, and 21% of the core study participants did not enter the extension, which may have affected the results.Conclusions:Gains in patient-reported visual function at month 12 among eyes receiving ranibizumab in the core study decreased slightly by 36 months. Eyes originally receiving laser monotherapy for 12 months then ranibizumab for 24 months achieved similar gains by 36 months to eyes receiving ranibizumab for 36 months.Trial Registration:ClinicalTrials.gov: NCT00687804 and NCT00906464.

Efficacy/safety of ranibizumab monotherapy or with laser versus laser monotherapy in DME

ObjectiveTo compare the efficacy and safety of ranibizumab 0.5 mg intravitreal injection, as monotherapy or in combination with laser, with laser monotherapy in patients with visual impairment caused by diabetic macular edema. DesignTwelve-month, multicentre, open-label, parallel-group, randomized, active-control study. ParticipantsA total of 220 (ranibizumab monotherapy: n = 75, ranibizumab + laser: n = 73, laser monotherapy: n = 72) patients with a diagnosis of type I or II diabetes and visual impairment caused by macular edema were included in the efficacy analysis. MethodsRanibizumab was initiated with a fixed loading phase of 3 monthly injections followed by as needed therapy until stable vision achievement. Efficacy end points were the change in best corrected visual acuity (BCVA), change in central retinal thickness (CRT) measured by optical coherence tomography, proportion achieving a 15-letter BCVA gain, and 12-month Visual Function Questionnaire-25 (VFQ-25) score. Safety was assessed with the incidence and severity of adverse events. ResultsAt 12 months, significant (p < 0.001) mean BCVA improvements were observed for both the ranibizumab monotherapy (+8.9 [95% confidence interval (CI) 7.0–10.7] letters) and the ranibizumab + laser (+8.2 [95% CI 6.0–10.4] letters) groups compared with the laser monotherapy group (+0.3 [95% CI –2.9 to 3.5] letters). Similarly, a better response in terms of CRT improvement, BCVA letter gain, and VFQ-25 was observed in both ranibizumab groups compared with laser monotherapy. The safety profile was comparable in the 2 ranibizumab groups. ConclusionsRanibizumab as monotherapy or combined with laser resulted in significantly higher improvements in visual acuity and vision-related quality of life at month 12 as compared with laser monotherapy.

The REVEAL Study: Ranibizumab Monotherapy or Combined with Laser versus Laser Monotherapy in Asian Patients with Diabetic Macular Edema

The primary study hypothesis was that ranibizumab 0.5 mg monotherapy or combined with laser is superior to laser monotherapy based on mean average change in best-corrected visual acuity (BCVA) over 12 months in Asian patients with visual impairment resulting from diabetic macular edema (DME). A 12-month, randomized, double-masked, multicenter, laser-controlled, phase III study. Three hundred ninety-six patients aged ≥18 years, with type 1 or 2 diabetes mellitus, BCVA of 78-39 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, and visual impairment resulting from DME. Patients were randomized to ranibizumab + sham laser (n= 133), ranibizumab + active laser (n= 132), or sham injection + active laser (n= 131). Ranibizumab/sham injections were administered on day 1 and continued monthly. As of month 3, monthly injections were continued if stable vision was not reached. Treatment was reinitiated if BCVA decreased because of DME progression. Active/sham laser was administered on day 1 and thereafter according to ETDRS guidelines. Average change in BCVA from baseline to months 1 through 12, central retinal subfield thickness (CRST), and safety over 12 months. Ranibizumab monotherapy or combined with laser was superior to laser in improving mean average change in BCVA from baseline to months 1 through 12 (+5.9 and+5.7 vs+1.4 letters). At month 12, greater proportion of patients gained ≥15 letters with ranibizumab and ranibizumab+laser compared with laser (18.8% and 17.8% vs 7.8%). Mean CRST reduced significantly from baseline to month 12 with ranibizumab (-134.6 μm) and ranibizumab+ laser (-171.8 μm) versus laser (-57.2 μm). Patients received a mean of 7.8 and 7.0 ranibizumab injections in the ranibizumab and ranibizumab + laser arms, respectively, and 1.5-1.9 active laser across treatment arms over 12 months. Conjunctival hemorrhage was the most common ocular, whereas nasopharyngitis and hypertension were the most common nonocular adverse events. Ranibizumab was not associated with any cases of cerebrovascular hemorrhage and cerebrovascular ischemia. No death related to study treatment was reported. Ranibizumab monotherapy or combined with laser showed superior BCVA improvements over laser treatment alone in Asian patients with visual impairment resulting from DME. No new ocular or nonocular safety findings were observed and treatment was well tolerated over 12 months.

Cost-effectiveness of non-surgical peri-implantitis treatments.

The purpose of the present study was to assess the cost-effectiveness of various alternatives of non-surgical peri-implantitis treatment. A decision analytical model was constructed and populated with parameter estimates from recent literature for reduction in pocket probing depth (PPD) in response to eight different treatment alternatives. A micro-costing approach combined with an online expert survey was applied to simulate a decision-making scenario taking place in Germany. The treatment alternatives providing the most advantageous cost/outcome combinations were identified according to the net benefit criterion. Uncertainties regarding model input parameters were incorporated via simple and probabilistic sensitivity analysis based on Monte Carlo simulation. In the base case scenario, debridement alone, Air-Flow, debridement combined with PerioChip, and debridement combined with local antibiotics were identified as treatment strategies with comparably better value for money than Er:YAG laser monotherapy, Vector System, debridement combined with CHX, and photodynamic therapy. Sensitivity analysis revealed considerable decision uncertainty corresponding to limited evidence about different treatment alternatives for peri-implantitis treatment. Derivation of robust treatment recommendations for peri-implantitis requires more comprehensive and patient-centred evidence on peri-implantitis treatments.