Daniele Veritti

Nonvisible subthreshold micropulse diode laser (810 nm) treatment of central serous chorioretinopathy: A pilot study

Purpose To verify the efficacy of nonvisible micropulse diode laser irradiation in the treatment of central serous chorioretinopathy (CSC). Methods Twenty-two patients with CSC for a total of 24 eyes with a disease duration longer than 3 months were included in a prospective study. Patients underwent Early Treatment Diabetic Retinopathy Study visual acuity (VA) examination, dilated ophthalmoscopy fluorescein angiography and optical coherence tomography before treatment and during follow-up. Treatment with a micropulse diode laser was given with a duty cycle of 15%. Multiple spots were placed over and adjacent to the area of retinal pigment epithelium leak or decompensation. Results Mean follow-up was 14 months (range 3–36 months). Powers used ranged from 1 to 2 W (mean 1.35 W). Mean number of spots was 215 (range 90–400). Fourteen eyes were treated once, nine eyes received two to three treatments, and one eye had five treatments during a follow-up of 3 years. Subretinal fluid was resolved or improved in two third of cases 1 month after laser treatment, and in three-quarters at the end of follow-up. Mean retinal thickness was 328 μm, 197 μm, and 168 μm before, 1 month after irradiation, and at the end of follow-up, respectively. No evidence of RPE or retinal changes due to laser treatment were discernible in most of the eyes. Median VA was 20/32 (range 20/100–20/20) before treatment and 20/25 (range 20/200–20/20) at the end of the follow-up. Conclusions Nonvisible micropulse diode laser may have efficacy in the treatment of CSC. A randomized study with larger series is needed.

Neovascular Age-Related Macular Degeneration

Purpose: Neovascular age-related macular degeneration (AMD) is a leading cause of blindness, with an increasing incidence as the elderly population expands. Large, multi-center, randomized, clinical trials have been conducted exploring the safety and efficacy of anti-VEGF treatments. This paper aims to discuss the safety and efficacy of pegaptanib, ranibizumab, aflibercept and bevacizumab. New therapeutic agents and treatment strategies are also discussed. Procedures: Evidence available from prospective, multicenter, clinical studies and from a selective literature search is utilized to present the results of VEGF inhibition in neovascular AMD and to generate evidence-based recommendations. Results: Anti-VEGF treatment is indicated in choroidal neovascularization with active disease and produces a significant benefit in visual acuity. Conclusions: With the advent of anti-VEGF therapy, the prognosis of choroidal neovascularization has changed dramatically. Data from well-conducted clinical trials suggest that approved anti-VEGF drugs are effective and well tolerated.

Intravitreal Steroids for the Treatment of Retinal Diseases

Diabetic macular edema (DME), pseudophakic cystoid macular edema (CME), age-related macular degeneration (AMD), retinal vascular occlusion (RVO), and uveitis are ocular conditions related to severe visual impairment worldwide. Corticosteroids have been widely used in the treatment of these retinal diseases, due to their well-known antiangiogenic, antiedematous, and anti-inflammatory properties. Intravitreal steroids have emerged as novel and essential tools in the ophthalmologists armamentarium, allowing for maximization of drug efficacy and limited risk of systemic side effects. Recent advances in ocular drug delivery methods led to the development of intraocular implants, which help to provide prolonged treatment with controlled drug release. Moreover, they may add some potential advantages over traditional intraocular injections by delivering certain rates of drug directly to the site of action, amplifying the drugs half-life, contributing in the minimization of peak plasma levels of the drug, and avoiding the side effects associated with repeated intravitreal injections. The purpose of this review is to provide an update on the use of intravitreal steroids as a treatment option for a variety of retinal diseases and to review the current literature considering their properties, safety, and adverse events.

Different antivascular endothelial growth factor treatments and regimens and their outcomes in neovascular age-related macular degeneration: a literature review.

Antivascular endothelial growth factor (anti-VEGF) therapy has revolutionised the treatment of wet age-related macular degeneration (wAMD). Recent research has focused on evaluating competing agents and alternative dosage regimens, providing evidence to help determine optimal treatment strategies. We therefore conducted a review of clinical research studies in wAMD published since 2008 that compared anti-VEGF dosing regimens and therapies; seven studies met our inclusion criteria. Data on baseline disease characteristics, disease outcomes, safety (ocular and systemic) and treatment burden (injection and visit frequencies) were extracted on patients treated with ranibizumab 0.5 mg, bevacizumab 1.25 mg or aflibercept 2.0 mg for up to 2 years. For ranibizumab and bevacizumab, visual and anatomical outcomes at 1 and 2 years were superior using scheduled monthly (or 4 weekly (q4w)) compared with as needed or scheduled quarterly dosing regimens. Treatment outcomes were generally better for both drugs when more aggressive retreatment criteria were used, which resulted in more frequent injections. Bevacizumab, however, was associated with a 30–35% elevated rate of serious systemic adverse events compared with ranibizumab, regardless of dosing interval; further study in larger patient populations will be required to determine the validity of this finding. Intravitreal aflibercept injection every 8 weeks was non-inferior to ranibizumab q4w on all visual and anatomical endpoints at week 52, had a similar safety profile and required five fewer anti-VEGF injections.

Drug safety evaluation of intravitreal triamcinolone acetonide

Introduction: Triamcinolone acetonide (TA) is a steroidal drug that has been widely administered intravitreally for retinal and choroidal conditions. Safety of steroidal products for intraocular use is essential because of their risk of ocular adverse events. This review comprehensively discusses the safety of intravitreal administration of TA. Areas covered: This paper analyzes the mechanisms of action and key pharmacokinetic attributes and provides a discussion of the main clinical trials investigating clinical applications of intravitreal TA. The safety of intravitreal TA is evaluated through a search of the Medline database from 1980 to 2011. The most relevant literature on the safety of intravitreal TA is also discussed. Expert opinion: The complications of intravitreal TA therapy include secondary ocular hypertension in about 20 – 40% of eyes, steroid-induced cataract in about 15 – 20% of cases and postinjection infectious endophthalmitis and pseudoendophthalmitis in less than 1%. TA is an effective drug for various retinal and choroidal diseases when delivered intravitreally. It may imply an off-label use and it may be associated with ocular adverse events. Intravitreal TA is not associated with significant systemic safety risks.

Experience with the Pascal® photocoagulator: An analysis of over 1200 laser procedures with regard to parameter refinement

Aim: To systematically refine and recommend parameter settings of spot size, power, and treatment duration using the Pascal® photocoagulator, a multi-spot, semi-automated, short-duration laser system. Materials and Methods: A retrospective consecutive series with 752 Caucasian eyes and 1242 laser procedures over two years were grouped into, (1) 374 macular focal / grid photocoagulation (FP), (2), 666 panretinal photocoagulation (PRP), and (3) 202 barrage photocoagulation (BP). Parameters for power, duration, spot number, and spot size were recorded for every group. Results: Power parameters for all groups showed a non-gaussian distribution; FP group, median 190 mW, range 100 – 950 mW, and PRP group, median 800 mW, range 100 – 2000 mW. On subgroup comparison, for similar spot size, as treatment duration decreased, the power required increased, albeit in a much lesser proportion than that given by energy = power × time. Most frequently used patterns were single spot (89% of cases) in FP, 5 × 5 box (72%) in PRP, and 2 × 2 box (78%) in BP. Spot diameters as high as ≈ 700 μm on retina were given in the PRP group. Single session PRP was attempted in six eyes with a median spot count of 3500. Conclusion: Overall, due to the small duration of its pulse, the Pascal® photocoagulator tends to use higher powers, although much lower cumulative energies, than those used in a conventional laser. The consequent lesser heat dissipation, especially lateral, can allow one to use relatively larger spot sizes and give more closely spaced burns, without incurring significant side effects.

Advances in pharmacotherapy for wet age-related macular degeneration

Introduction: In developed countries, neovascular age-related macular degeneration (AMD) is the leading cause of irreversible central blindness. Although AMD pathogenesis is complex and still not fully understood, many involved mechanisms are already partially known and could be promising targets for future therapies. Currently, anti-VEGF drugs are the standard care of this condition. Areas covered: This review summarizes both the current available and the emerging pharmacological therapies for the management of neovascular AMD. At first, we briefly focused on anti-VEGF compounds that are commonly used. Then, we reviewed the mechanisms of action and potential advantages of new candidate drugs that are being evaluated in clinical trials. Expert opinion: Although anti-VEGF drugs have shown mild-term good efficacy and safety profile in the treatment of neovascular AMD, they are far away from being a perfect therapy. Pharmacological research should focus on finding new molecular targets in the AMD pathogenetical pathway and on developing longer lasting agents or new drug delivery systems. Besides the development of new drugs, a better characterization of patients is also needed, taking into account variables such as choroidal neovascularization subtypes and genetic factors, in order to identify a tailored treatment for each patient.

Bevacizumab and Triamcinolone Acetonide for Choroidal Neovascularization Due to Age-Related Macular Degeneration Unresponsive to Antivascular Endothelial Growth Factors

PURPOSE To evaluate the safety and efficacy of a combined approach using an antivascular endothelial growth factor (VEGF) agent (bevacizumab) and a steroid (triamcinolone acetonide) for treating choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) unresponsive to anti-VEGF monotherapy. METHODS Retrospective case series. We analyzed 25 eyes with CNV due to AMD who received a combination of intravitreal bevacizumab (1 mg) and triamcinolone (4 mg). Results were assessed at 7 days, 1, 3, 6, 9, and 12 months by best-corrected visual acuity (BCVA) measurement, fluorescein angiography, indocyanine green angiography, and optical coherence tomography (OCT). Retreatment with intravitreal bevacizumab or combination therapy was considered at investigator discretion at every follow-up visit. RESULTS A mean BCVA improvement of 0.18 (95% CI: 0.05; 0.3) logMAR was reported between baseline and the 12-month measurement (P<0.01). An opposite trend toward progressive loss of BCVA, from 1.08 to 1.31 logMAR, had been observed in the 6 months before starting the combination therapy, in spite of regular treatment with anti-VEGFs (P<0.0001). OCT measurements showed a 139-μm (95% CI: 76; 203) decrease in mean central retinal thickness (P<0.01). On average, patients required 1.8 additional treatments. Five (20%) cases of intraocular pressure elevation were successfully treated with medications. CONCLUSIONS Combination therapy with intravitreal bevacizumab and triamcinolone acetonide proved to be a safe and effective option for CNV unresponsive to anti-VEGF monotherapy. The combined treatment reversed the preoperative trend toward losing vision, and a significant anatomic improvement was seen by OCT.

INTRAVITREAL AFLIBERCEPT FOR CHOROIDAL NEOVASCULARIZATION DUE TO AGE-RELATED MACULAR DEGENERATION UNRESPONSIVE TO RANIBIZUMAB THERAPY.

Purpose: To assess the efficacy of intravitreal injection of aflibercept for treating choroidal neovascularization due to age-related macular degeneration unresponsive to ranibizumab. Methods: Prospective noncomparative study. Indication for conversion to aflibercept (2.0 mg) was a failed response to ranibizumab, defined as persistent or recurrent subretinal and/or intraretinal fluid on spectral domain optical coherence tomography. Best-corrected visual acuity (Early Treatment Diabetic Retinopathy Study letter score), fluorescein angiography, indocyanine green angiography, and spectral domain optical coherence tomography were performed at baseline. Patients were followed up monthly, and retreatment was considered at physician discretion based on functional and morphological patterns. Results: Ninety-two eyes were included in the study. At 12 months, mean best-corrected visual acuity (±SD) change was +1.8 (±10.3), Early Treatment Diabetic Retinopathy Study letters and central retinal thickness (±SD) decreased on average by 112 (±173) &mgr;m. Patients received a mean of 3.5 ± 1.8 injections. No significant adverse event was observed during the follow-up. Conclusion: A low number of intravitreal aflibercept injections reversed the preswitching trend toward losing vision and produced stable visual acuity and morphological improvements for up to 12 months in patients with neovascular age-related macular degeneration, not responding to ranibizumab.

Pharmacotherapy for treatment of retinal vein occlusion

Introduction: Retinal vein occlusion (RVO) is a common vascular condition, which may cause blindness and impaired vision as a result of the development of macular oedema. The management of macular oedema due to RVO is complex and a multidisciplinary approach is required in order to limit disease progression and achieve a better clinical outcome. Areas covered: An update and a brief review on the current treatment strategies were provided in patients with macular oedema following RVOs. Evidence available from prospective, multicentre clinical studies evaluating the use of VEGF inhibitors and steroids and from a selective literature search is reported. Expert opinion: For many years, laser photocoagulation has been considered the standard of care for the treatment of branch RVO. However, new treatment modalities have been evaluated through randomised controlled trials. Recently, anti-VEGF agents and corticosteroids have been shown to be efficacious options in the treatment of RVO.