Beatriz Sayuri Takahashi

Combined Laser and Intravitreal Triamcinolone for Proliferative Diabetic Retinopathy and Macular Edema: One-year Results of a Randomized Clinical Trial

PURPOSE To evaluate laser combined with intravitreal triamcinolone acetonide (IVTA) for the management of patients with proliferative diabetic retinopathy (PDR) and clinically significant macular edema (CSME). DESIGN Randomized clinical trial. METHODS settings: Single center. study population: Twenty-two patients with bilateral treatment-naïve moderate PDR and CSME. intervention: Laser (panretinal and macular) photocoagulation was performed in each eye, followed by IVTA in one randomly assigned eye. Best-corrected visual acuity (BCVA), fundus photography, and optical coherence tomography were performed at baseline and at months 1, 3, 6, 9, and 12. main outcome measures: Changes in BCVA, central macular thickness (CMT), and total macular volume (TMV). RESULTS The mean logarithm of the minimal angle of resolution (logMAR) BCVA improved significantly, and mean CMT and TMV were significantly reduced in the IVTA group compared with the laser-only group (controls) at all study follow-up visits (P < .001). The mean logMAR BCVA (Snellen equivalent) was 0.44 (20/50(-2)) for the IVTA group and 0.38 (20/50(+1)) for the controls at baseline, and 0.12 (20/25(-1)) for the IVTA group and 0.32 (20/40(-1)) for the controls at 12 months (P < .001). The mean CMT and TMV were, respectively, 360 microm and 8.59 mm(3) for the IVTA group and 331 microm and 8.44 mm(3) for the controls at baseline, and 236 microm and 7.32 mm(3) for the IVTA group and 266 microm and 7.78 mm(3) for the controls at 12 months (P < .001). CONCLUSIONS The combination of laser photocoagulation with IVTA was associated with improved BCVA and decreased CMT and TMV when compared with laser photocoagulation alone for the treatment of moderate PDR with CSME.

New approaches and potential treatments for dry age-related macular degeneration

Emerging treatments for dry age-related macular degeneration (AMD) and geographic atrophy focus on two strategies that target components involved in physiopathological pathways: prevention of photoreceptors and retinal pigment epithelium loss (neuroprotection induction, oxidative damage prevention, and visual cycle modification) and suppression of inflammation. Neuroprotective drugs, such as ciliary neurotrophic factor, brimonidine tartrate, tandospirone, and anti-amyloid β antibodies, aim to prevent apoptosis of retinal cells. Oxidative stress and depletion of essential micronutrients are targeted by the Age-Related Eye Disease Study (AREDS) formulation. Visual cycle modulators reduce the activity of the photoreceptors and retinal accumulation of toxic fluorophores and lipofuscin. Eyes with dry age-related macular degeneration present chronic inflammation and potential treatments include corticosteroid and complement inhibition. We review the current concepts and rationale of dry age-related macular degeneration treatment that will most likely include a combination of drugs targeting different pathways involved in the development and progression of age-related macular degeneration.

Experimental models of autoimmune inflammatory ocular diseases

Ocular inflammation is one of the leading causes of blindness and loss of vision. Human uveitis is a complex and heterogeneous group of diseases characterized by inflammation of intraocular tissues. The eye may be the only organ involved, or uveitis may be part of a systemic disease. A significant number of cases are of unknown etiology and are labeled idiopathic. Animal models have been developed to the study of the physiopathogenesis of autoimmune uveitis due to the difficulty in obtaining human eye inflamed tissues for experiments. Most of those models are induced by injection of specific photoreceptors proteins (e.g., S-antigen, interphotoreceptor retinoid-binding protein, rhodopsin, recoverin, phosducin). Non-retinal antigens, including melanin-associated proteins and myelin basic protein, are also good inducers of uveitis in animals. Understanding the basic mechanisms and pathogenesis of autoimmune ocular diseases are essential for the development of new treatment approaches and therapeutic agents. The present review describes the main experimental models of autoimmune ocular inflammatory diseases.

Vitreous pharmacokinetics and electroretinographic findings after intravitreal injection of acyclovir in rabbits

OBJECTIVES: Acute retinal necrosis is a rapidly progressive and devastating viral retinitis caused by the herpesvirus family. Systemic acyclovir is the treatment of choice; however, the progression of retinal lesions ceases approximately 2 days after treatment initiation. An intravitreal injection of acyclovir may be used an adjuvant therapy during the first 2 days of treatment when systemically administered acyclovir has not reached therapeutic levels in the retina. The aims of this study were to determine the pharmacokinetic profile of acyclovir in the rabbit vitreous after intravitreal injection and the functional effects of acyclovir in the rabbit retina. METHODS: Acyclovir (Acyclovir; Bedford Laboratories, Bedford, OH, USA) 1 mg in 0.1 mL was injected into the right eye vitreous of 32 New Zealand white rabbits, and 0.1 mL sterile saline solution was injected into the left eye as a control. The animals were sacrificed after 2, 9, 14, or 28 days. The eyes were enucleated, and the vitreous was removed. The half-life of acyclovir was determined using high-performance liquid chromatography. Electroretinograms were recorded on days 2, 9, 14, and 28 in the eight animals that were sacrificed 28 days after injection according to a modified protocol of the International Society for Clinical Electrophysiology of Vision. RESULTS: Acyclovir rapidly decayed in the vitreous within the first two days after treatment and remained at low levels from day 9 onward. The eyes that were injected with acyclovir did not present any electroretinographic changes compared with the control eyes. CONCLUSIONS: The vitreous half-life of acyclovir is short, and the electrophysiological findings suggest that the intravitreal delivery of 1 mg acyclovir is safe and well tolerated by the rabbit retina.

Three-monthly intravitreal bevacizumab injections for neovascular age-related macular degeneration: short-term visual acuity results.

Purpose. To evaluate the change in vision after 3 monthly consecutive intravitreal injections of 1.25 mg of bevacizumab for neovascular age-related macular degeneration (AMD). Methods. A retrospective analysis of 35 eyes was performed. Visual acuity (VA) at initial visit and at each follow-up visit was compared. The injection of bevacizumab was performed at 30-day intervals and patients were observed for 5 months after the last injection. Results. Of the 35 eyes, 9 had received previous treatment with photodynamic therapy with or without 4 mg of intravitreal triamcinolone. VA was measured in Snellen table and transformed into logMAR for statistical purposes. Mean age was 76.66 years (range, 49–90 years). There were 24 (69%) women and 11 (31%) men. Mean VA at the initial visit was 0.92±0.50. At month 1, mean VA was 0.84±0.51 and at month 2 was 0.74±0.51. At month 3, mean VA remained 0.74±0.49. Six and 8 months after the initial visit, VA was 0.79±0.49 and 0.77±0.50, respectively. The improvement in VA was statistically significant at month 2 and at the end of the follow-up (8 months) compared with the baseline VA. Conclusions. Three consecutive monthly injections of intravitreal bevacizumab to treat neovascular AMD is effective in improving VA in the short term. Longer prospective studies should be performed to confirm VA stability after the third injection.

Transscleral delivery of Nd: YLF laser at 1,047 nm causes vascular occlusion in experimental pigmented choroidal melanoma.

Purpose: The aims of this study were to determine the scleral attenuation of focused neodymium: yttrium–lanthanum–fluoride laser at 1,047 nm applied transsclerally and whether transscleral delivery can close the vascular supply at the base of experimental choroidal melanoma in rabbits. Methods: Fifty-two New Zealand albino rabbits were included. Scleral laser attenuation was measured across fresh sclera. B16F10 melanomas were established in the subchoroidal space of 49 rabbits. Twenty-one animals were killed immediately after transscleral treatment, 14 were followed for 2 weeks to 4 weeks, and 14 were followed without treatment. Ophthalmoscopy, fundus photographs, and fluorescein angiography were performed before treatment, immediately after, and weekly during the follow-up. Eyes were examined by light microscopy. Results: Sclera attenuated laser energy by 31% ± 7%. Immediately after treatment, angiography showed diffuse hypofluorescence in 71% (15 of 21 rabbits). Light microscopy showed vascular occlusion extending at least two thirds of the tumor thickness from the base. Seven of the 14 tumors followed for 15 days ± 8 days were eradicated. There was no correlation between tumor height and eradication. Conclusion: Rabbit sclera attenuated 31% ± 7% of laser energy. A single transscleral treatment causes tumor vascular closure at the base and may serve as an adjuvant therapy to ensure destruction of deep and intrascleral tumor cells.

Use of intravitreal bevacizumab or triamcinolone acetonide as a preoperative adjunct to vitrectomy for vitreous haemorrhage in diabetics

PURPOSE: To evaluate the effect of preoperative intravitreal bevacizumab (IVB) or triamcinolone (IVT) on the rate of early postvitrectomy hemorrhage in proliferative diabetic retinopathy (PDR). METHODS: Eligible eyes were assigned randomly to 1 of 3 groups: the IVB group received 1.25 mg bevacizumab, the IVT group received 4,0mg triamcinolone and the control group underwent a sham procedure. The primary outcome measure was the incidence of early postvitrectomy hemorrhage. Secondary outcome measures included changes in visual acuity (BCVA) and adverse events. RESULTS: Twenty and seven eyes, 9 in each group were randomized. The incidence of vitreous hemorrhage was lower in the IVB group (p=0.18). Postoperative vitreous hemorrhage at 1 month also was less in the IVB group compared with the control group (p > 0.05). The rate of bleeding immediately after surgery was higher in IVT group with 4 (44.4%) cases. The overall mean visual acuity was 1.72 ± 0.37 logMAR preoperatively and 1.32 ± 0.73 logMAR in 6 months after surgery. Accessing visual acuity by group evidenced that the IVB group had initial mean logMAR VA of 1.87 and 1.57 logMAR VA at the six months (p = 0.84). In IVT group, initial mean VA was 1.75 logMAR and 0.96 logMAR VA at six months (p < 0.001). And in control group, the initial mean VA was 1.85 logMAR and 1.57 logMAR VA at six months (p= 0.34). CONCLUSION: Intravitreal injection of bevacizumab 1 week before vitrectomy seems to reduce the incidence of early postvitrectomy hemorrhage in diabetic patients. There was a better visual acuity outcome in the triamcinolone group.

Verteporfin photodynamic therapy in the age of antiangiogenic therapy

Photodynamic therapy with verteporfin was the first approved pharmacological treatment for choroidal neovascularization in patients with age-related macular degeneration, pathologic myopia and ocular histoplasmosis syndrome. With the introduction of anti-VEGF therapy, verteporfin photodynamic therapy is no longer the first line of treatment for neovascular age-related macular degeneration. Ongoing clinical trials will determine the future role of PDT alone or as part of a more individualized combination therapy.

Estudo macular em olhos com óleo de silicone por meio da tomografia de coerência óptica

PURPOSE: To demonstrate optical coherence tomography efficacy to evaluate macular anatomical outcomes, in eyes with silicone oil-filled vitreous cavity after vitrectomy. METHODS: A descriptive observational study of 28 (twenty-eight) patients submitted to pars plana vitrectomy having silicone oil as vitreous substitute. The macular findings were observed by means of indirect binocular ophthalmoscope, biomicroscopy and optical coherence tomography examinations. RESULTS: During the follow-up period the retina remained attached in all patients. In some cases, intraretinal cysts, epiretinal membrane and lamellar macular hole were observed only by optical coherence tomography examination. CONCLUSION: Optical coherence tomography provided improved imaging of finer retinal structures in eyes with silicone oil-filled vitreous cavity. Therefore, optical coherence tomography examination should be systematically performed in eyes filled with silicone oil to recognize changes in retinal morphology.PURPOSE To demonstrate optical coherence tomography efficacy to evaluate macular anatomical outcomes, in eyes with silicone oil-filled vitreous cavity after vitrectomy. METHODS A descriptive observational study of 28 (twenty-eight) patients submitted to pars plana vitrectomy having silicone oil as vitreous substitute. The macular findings were observed by means of indirect binocular ophthalmoscope, biomicroscopy and optical coherence tomography examinations. RESULTS During the follow-up period the retina remained attached in all patients. In some cases, intraretinal cysts, epiretinal membrane and lamellar macular hole were observed only by optical coherence tomography examination. CONCLUSION Optical coherence tomography provided improved imaging of finer retinal structures in eyes with silicone oil-filled vitreous cavity. Therefore, optical coherence tomography examination should be systematically performed in eyes filled with silicone oil to recognize changes in retinal morphology.

Bilateral choroidal neovascularization response to unilateral intravitreal Ranibizumab injection in a patient with angioid streaks

Os autores descrevem paciente do sexo masculino, 48 anos, com diminuicao visual bilateral ha 15 dias por membrana neovascular sub-retiniana secundaria a estrias angioides. A acuidade visual com melhor correcao no olho direito era 20/80 e no olho esquerdo de conta dedos a 2 metros. Submetido a injecao intravitrea de Ranibizumabe (Lucentis) no olho com pior acuidade visual. Apos 15 dias do tratamento, referiu melhora acentuada da visao no olho contralateral com visao de 20/25. O resultado foi avaliado por meio da acuidade visual e da tomografia de coerencia optica. O efeito do ranibizumabe foi observado no olho tratado, mas no olho contralateral houve completa resolucao do complexo da membrana neovascular sub-retiniana. Levanta-se a hipotese de que esse resultado possa ser atribuido a absorcao sistemica da medicacao.