Corrado Balacco Gabrieli

Mitochondrial alterations of retinal pigment epithelium in age-related macular degeneration

Mitochondrial dysfunctions have been implicated in the pathophysiology of several age-related diseases including age-related macular degeneration (AMD), a progressive neurodegenerative disease affecting primarily the retinal pigment epithelium (RPE). The aims of our electron microscopic and morphometric studies were to reveal qualitative and quantitative alterations of mitochondria in human RPE from AMD and from age- and sex-matched controls. With increasing age a significant decrease in number and area of mitochondria, as well as loss of cristae and matrix density were found in both AMD and control specimens. These decreases were significantly greater in AMD than in normal aging. Alterations of mitochondria were accompanied by proliferation of peroxisomes and lipofuscin granules in both AMD and control specimens, although the difference between groups was significant only for peroxisomes. Unexpectedly, morphometric data showed that the RPE alterations seen in AMD may also develop in normal aging, 10-15 years after appearing in AMD patients. These findings suggest that (i) the severity of mitochondrial and peroxisomal alterations are different between AMD and normal aging, and (ii) the timing of damage to RPE may be critical for the development of AMD. We conclude that besides the well-documented age-related changes in mitochondrial DNA, alterations of mitochondrial membranes may also play a role in the pathogenesis of AMD. These membranes could be a new target for treatment of AMD and other age-related diseases.

Intravitreal Bevacizumab Treatment for Choroidal Neovascularization in Pathologic Myopia: 12-month Results

PURPOSE To evaluate the short-term efficacy and safety of intravitreal bevacizumab for the treatment of myopic choroidal neovascularization (CNV). DESIGN Prospective, nonrandomized, interventional case series. METHODS Twenty eyes from 20 patients with CNV secondary to pathologic myopia participated in this prospective nonrandomized interventional case series. All patients were scheduled for three monthly intravitreal bevacizumab 1.25 mg injections. Early Treatment Diabetic Retinopathy Study best-corrected visual acuity (BCVA), foveal center thickness (FCT) on optical coherence tomography (OCT), and fluorescein angiographic findings were examined before and after treatment. Patients were followed up for 12 months. RESULTS The mean BCVA (+/- standard deviation [SD]) at baseline was 24.8 (+/- 11.86) letters (Snellen equivalent: 20/80). At 12 months after treatment, the mean BCVA (+/- SD) improved significantly (P = .000001) to 43 (+/- 12.38) letters (Snellen equivalent: 20/35). At 12 month follow-up, BCVA improved 10 letters or more in 18 (90%) out of 20 treated eyes and improved 15 letters or more in 14 (70%) out of 20 treated eyes. No treated eyes experienced a worsening of BCVA from baseline. The mean FCT (+/- SD) at baseline was 223 (+/- 47.43) microns. At 12 months after treatment, the mean FCT (+/- SD) reduced to 206 (+/- 50.87) microns. This reduction in FCT after treatment was not statistically significant (P = .11). At 12 months follow-up, absence of fluorescein leakage from the CNV was demonstrated in 19 (95%) out of 20 treated eyes and persistent leakage in one eye (5%). None of the 19 eyes that had CNV closure experienced recurrence at 12-month follow-up. No ocular or systemic adverse effects from treatment were encountered. CONCLUSION These results of intravitreal bevacizumab in myopic CNV are very promising with no apparent short-term safety concerns. At 12 months, treated eyes had a significant improvement in visual acuity (VA). OCT findings, as well, showed a trend consistent with the beneficial changes observed for VA. Treatment resulted in complete absence of angiographic leakage in 95% of eyes. Further studies will be needed to better determine long-term efficacy and safety.

Choroidal Neovascularization in Pathologic Myopia: Intravitreal Ranibizumab Versus Bevacizumab—A Randomized Controlled Trial

PURPOSE To compare the short-term efficacy and safety of intravitreal ranibizumab versus bevacizumab in treating myopic choroidal neovascularization (CNV). DESIGN Prospective, comparative, randomized, interventional study. METHODS Thirty-two eyes from 32 patients with myopic CNV were consecutively enrolled and randomly treated, in a 1:1 ratio, with intravitreal ranibizumab (0.5 mg) or bevacizumab (1.25 mg) as needed, after the first injection. ETDRS best-corrected visual acuity (BCVA), foveal center thickness (FCT) on optical coherence tomography (OCT), and fluorescein angiographic findings were examined before and after treatment. Patients were followed up for 6 months. RESULTS No statistically significant difference in the BCVA improvement, as well as in the FCT reduction, was found between groups during follow-up (P value at 1, 3, 6 months > .05). Complete resolution of fluorescein leakage was observed in all 16 bevacizumab-treated eyes and in 15 out of 16 (93.7%) ranibizumab-treated eyes. No ocular or systemic adverse effects from treatment were encountered. CONCLUSION This randomized clinical study cannot determine a statistically significant difference in anti-VEGF treatment effect between ranibizumab and bevacizumab for the treatment of CNV secondary to pathologic myopia. A larger study is required to determine the relative efficacy and duration of action of these drugs.

Correlation between spectral-domain optical coherence tomography findings and visual outcome after primary rhegmatogenous retinal detachment repair.

Purpose: To correlate the postoperative visual outcome with the spectral-domain optical coherence tomography (SD-OCT) findings in the fovea after successful rhegmatogenous retinal detachment repair. Cross-sectional, observational study. Methods: Thirty-five patients with preoperative macula-on rhegmatogenous retinal detachment (12 eyes) and macula-off rhegmatogenous retinal detachment (23 eyes) who underwent scleral buckling surgery for primary rhegmatogenous retinal detachment were recruited. Early Treatment Diabetic Retinopathy Study best-corrected visual acuity measurement, microperimetry, and SD-OCT examination were performed on the same day. Foveal center retinal thickness, central 1-mm subfield thickness, and outer nuclear layer thickness were measured using SD-OCT. The presence or absence of epiretinal membrane, intraretinal fluid, and subretinal fluid was assessed. The status of the external limiting membrane, inner/outer segment junction, and intermediate line was also evaluated and judged as disrupted or complete. The correlations between SD-OCT findings and either postoperative best-corrected visual acuity or retinal sensitivities for central 12° were analyzed. Results: The outer nuclear layer thickness was the only significant SD-OCT retinal measurement strongly correlated with both postoperative best-corrected visual acuity (r = 0.61; P < 0.001) and retinal sensitivities for central 12° (r = 0.53; P = 0.001). Among the SD-OCT imaging findings, status of the external limiting membrane, inner/outer segment junction, and intermediate line and the presence of intraretinal fluid showed a significantly high correlation either with best-corrected visual acuity outcome (r = −0.60; P < 0.001, r = −0.63; P < 0.001, r = −0.66; P < 0.001, and r = −0.50; P = 0.002, respectively) or with postoperative retinal sensitivities (r = −0.59; P < 0.001, r = −0.61; P < 0.001, r = −0.66; P < 0.001, r = −0.50; P = 0.002, respectively). Multivariate analysis showed that the outer nuclear layer thickness and the status of the intermediate line were the most important predictors of visual outcome (P < 0.001 and P < 0.001, respectively). Conclusion: This study showed that not only the status of the external limiting membrane and the inner/outer segment junction but also the integrity of the intermediate line and the outer nuclear layer thickness changes may be important predictors of postoperative visual outcome after anatomically successful rhegmatogenous retinal detachment repair.

Intravitreal Bevacizumab As Primary Treatment For Retinal Angiomatous Proliferation: Twelve-month Results

Purpose: To evaluate the short-term efficacy and safety of intravitreal bevacizumab for the treatment of retinal angiomatous proliferation. Methods: Seventeen eyes from 16 patients with newly diagnosed retinal angiomatous proliferation underwent intravitreal injections of bevacizumab, 1.25 mg. The patients were scheduled for three monthly bevacizumab injections. Early Treatment of Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity, central macular thickness on optical coherence tomography, and fluorescein angiographic findings were examined before and after treatment. Patients were followed-up for 12 months. Results: The mean best-corrected visual acuity (± standard deviation [SD]) at baseline was 39.53 (±10.40) letters (Snellen equivalent: 20/42). At 12 months after treatment the mean best-corrected visual acuity (±SD) improved significantly (P = 0.0000001) to 47.88 (±11.78) letters (Snellen equivalent: 20/28). Best-corrected visual acuity improved 3 ETDRS lines or more in 3 (17.65%) of 17 treated eyes, 14 (82.35%) eyes were stable, and 15 (88.23%) eyes gained 1 or more ETDRS lines. The mean central macular thickness (±SD) at baseline was 297 (±60.72) &mgr;m. At 12 months after treatment, the mean central macular thickness (±SD) reduced significantly (P = 0.00001) to 237 (±28.80) &mgr;m. At the 12-month follow-up, absence of fluorescein leakage was demonstrated in 14 (82%) of 17 treated eyes. No ocular or systemic adverse effects from treatment were encountered. Conclusion: The 12-month results of intravitreal bevacizumab for retinal angiomatous proliferation are very promising with no apparent short-term safety concerns. Treated eyes had a significant functional and anatomical improvement. Further studies will be needed to better determine long-term efficacy and safety.

Subjective visual halos after sildenafil (Viagra) administration: Electroretinographic evaluation.

PURPOSE The ophthalmologic and electroretinographic (ERG) findings in one subject with subjective visual disturbances after sildenafil administration are described. DESIGN Interventional case report. METHODS A complete ophthalmologic examination was performed, including best-corrected visual acuity and ERG, repeated 1 and 2 hours after administration of 100 mg of sildenafil. MAIN OUTCOME MEASURES Rod responses were obtained over a range of retinal illuminances from those producing a minimum detectable response to those producing rod saturation. Intensity amplitude function was determined. RESULTS At 2 hours after 100 mg of oral sildenafil, we observed significant variations from baseline in parameters of best-fit Naka-Rushton function; V(max) was notably higher, and K was 0.14 log units lower than baseline. CONCLUSIONS Sildenafil administration resulted in a higher rod response to light stimuli and in a higher rod sensitivity. These findings are consistent with the weak PDE-6 inhibition induced by sildenafil.

Acute electroretinographic changes during sildenafil (Viagra) treatment for erectile dysfunction.

The authors describe their findings on 12 subjects who were treated with 50 mg of Sildenafil (Viagra) and underwent ERG measurements prior to and 1 hour after ingestion. The Naka–Rushton equation was used to describe the b-wave luminance-response function of the scotopic ERG. Statistically significant differences were noted in the Vmax and K values. Sildenafil ingestion resulted in an increase in Vmax (higher rod response to light stimuli) and a decrease in K (higher sensitivity).

Transient visual symptoms in systemic lupus erythematosus and antiphospholipid syndrome.

PURPOSE: To review the potential pathogenic mechanisms of transient visual symptoms (TVS) in the course of systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), to discuss the most common clinical features associated with the occurrence of TVS, and to explore possible treatment options for these patients. METHODS: The literature regarding the clinical and laboratory characteristics of SLE and APS patients experiencing TVS is reviewed from 1979 onward. A brief review of the wide spectrum of ophthalmologic features occurring in SLE and APS is also provided. RESULTS: Data emerging from the review process point to thromboembolism as the most probable cause of TVS in SLE and APS. Thromboembolisms are likely induced by cardiac valve abnormalities and should be treated with anticoagulant drugs. CONCLUSION: While progress has been made in understanding the association of TVS with SLE and APS, further investigation is needed to clarify this interesting relationship.

Fox's modified technique using the Mersilene mesh sling in the management of blepharoptosis.

BACKGROUND AND OBJECTIVE Frontalis suspension is the best surgical procedure for severe ptosis with poor or absent levator muscle function. In addition to autologous fascia lata, a variety of materials are available for suspension. The authors describe the use of Mersilene mesh slings developed to overcome the problems of failure, slippage, and extrusion commonly associated with various suspensory materials. PATIENTS AND METHODS Brow suspension was performed in 20 ptotic eyelids of 14 patients. All patients had severe ptosis with levator function of 4 mm or less. The surgical technique used was a modified version of the method originally described by Fox using the Mersilene mesh sling. RESULTS The improvement in lid height was evaluated by preoperative and postoperative vertical aperture measurements and ranged from 2 to 5 mm (average 3.5 mm). The results were maintained in all cases during a follow-up period of 18 months. CONCLUSION The good functional and cosmetic results suggest that Foxs modified technique using the Mersilene mesh sling has a definite place in ptosis management.

Use of Erbium:YAG Laser in the Treatment of Palpebral Xanthelasmas

OBJECTIVE In light of the research and the use of lasers in the therapy of xanthelasmas, the authors report their experience in the treatment of this pathology with Erbium:YAG laser. MATERIALS AND METHODS In 30 patients, all female, 70 xanthelasmas were treated with Erbium:YAG laser, 65 (93%) of which were on the upper eyelid and 5 (7%) on the lower eyelid, varying from 1 x 1.5 mm to 11 X 20 mm in size. Spots with a diameter of 1.6 mm, energy of 300 mJ, frequency of 1-5 Hz and in a number varying were used in relation to the extent of the pathology. RESULTS In all cases, the appearance and functional results were good, without leaving scars and/or dyschromia. CONCLUSIONS Erbium:YAG laser, in the treatment of xanthelasmas, is a parasurgical method that is simple to perform and because of the successful aesthetic and functional results, is a valid alternative to the more traditional treatment methods.