Evaluation of vitreous clearance and potential retinal toxicity of intravitreal lornoxicam (xefo).

PURPOSE: To evaluate the vitreous clearance and toxicological profile of commercially available lornoxicam (Xefo), after a single intravitreal injection in rabbits. METHODS: Twenty-five male albino rabbits (10 rabbits were used for retinal toxicity evaluation, while 15 rabbits were used to evaluate vitreous clearance) were used in this study. Two concentrations of lornoxicam were tested for retinal toxicity: 250 µg/0.1 mL and 1,500 µg/0.1 mL. Each concentration was intravitreally injected randomly in 1 eye of each rabbit (group I received 250 µg/0.1 mL, n=5 and group II received 1,500 µg/0.1 mL, n=5), while in the other eye 0.1 mL of sterile balanced saline solution was injected. Slit-lamp and funduscopic examinations along with intraocular pressure measurements (IOP) were performed prior to injection and at days 1, 15, and 30 after the injection for signs of infection, inflammation, toxicity, and IOP changes. A baseline electroretinogram (ERG) was performed before the experiment and at days 1, 15, and 30 after the intravitreal injection. At the last follow-up day, the animals were sacrificed and the enucleated eyes were prepared for histological evaluation of the retina. Lornoxicam (concentration of intravitreal injection: 250 µg/0.1 mL) clearance from the vitreous was estimated using high-performance liquid chromatography in 30 rabbit eyes. RESULTS: There were no statistical differences between the control and experimental eyes, concerning ERG amplitudes and IOP measurements for both groups (I and II), at all examinations. On the contrary, histological examination of the samples revealed extended retinal damage of group II experimental eyes (morphological alterations at the level of the inner nuclear and outer plexiform layers was evident along with disappearance of normal stratification of outer retina with vacuolization and thinning), whereas the morphology of group I experimental eyes did not differ from that of the control eyes. Lornoxicam is eliminated from the vitreous by a first-order kinetic process with a half-life of 1.7 h. CONCLUSIONS: Intravitreal lornoxicam causes dose-related toxic effect to the retina at a concentration of 1,500 µg. A dose of 250 µg does not seem to cause histological toxic effects at the level of the retina. Lornoxicam could be considered with interest for further research for the development of alternative treatments for ocular inflammatory conditions.

Contact transcleral photodynamic cyclo-suppression in human eyes: a feasibility study.

OBJECTIVE: To evaluate the safety and efficacy of contact transcleral ciliary body photodynamic treatment (CB-PDT) with verteporfin in human eyes. DESIGN: Prospective interventional case series. PARTICIPANTS: Five glaucomatous blind eyes of 5 patients. METHODS: Verteporfin (6 mg/m(2)) was infused in bolus and then the ciliary body was irradiated transclerally with a fibre optic device. Twelve spots were placed 360° and 0.5 mm behind the sclerocorneal limbus. Laser power was 80 mW and irradiation time was 3 minutes. RESULTS: The average intraocular pressure reduction was 30% after the first month and remained below pre-treatment levels throughout a 3-month follow-up. No serious adverse events were reported. CONCLUSIONS: CB-PDT for refractory glaucoma was safe and efficient in human eyes; larger studies are required to evaluate its possible clinical role.

Atorvastatin for diabetic macular edema in patients with diabetes mellitus and elevated serum cholesterol.

BACKGROUND AND OBJECTIVE: To determine the efficacy of atorvastatin in reducing hard exudates and diabetic macular edema. PATIENTS AND METHODS: An uncontrolled clinical case series included 18 eyes with diabetic maculopathy and an elevated baseline lipid profile. All patients were treated with atorvastatin. Ophthalmologic evaluation, including fundus photography and fluorescein angiography, was performed at presentation and repeated at 3, 6, and 12 months. Hard exudates, hemorrhages, and fluorescein leakage at 12 months were evaluated and compared with baseline findings. RESULTS: Eighteen subjects with diabetic maculopathy received atorvastatin, and a significant decrease in total cholesterol and low-density lipoprotein cholesterol was seen (P < .05). Hard exudates and fluorescein leakage were decreased. No evidence of an association between change in hemorrhage status and treatment was found. CONCLUSION: Oral atorvastatin therapy in patients with diabetes mellitus and dyslipidemia seems to reduce the severity of hard exudates and fluorescein leakage in diabetic maculopathy and could be useful as an adjuvant therapy in the management of diabetic macular edema.

Contact transcleral ciliary body photodynamic therapy with verteporfin in pigmented rabbits: effect of repeated treatments.

We studied the effect on the intraocular pressure (IOP) and the ciliary body (CB) morphology after four consecutive contact transcleral photodynamic treatments of the ciliary body (CB-PDT) with verteporfin in pigmented rabbits. Twenty-two pigmented rabbits underwent CB-PDT (study group), performed once (six rabbits) or repeated for up to four times (16 rabbits). Six additional rabbits received only laser treatment without photosensitizer administration (control group). CB-PDT was performed in one eye in rabbits of the study group, with the fellow eye serving as internal control. Verteporfin dosage was 1 mg kg(-1) as bolus injection and laser settings were 40 mW (600 microm core optical fiber) for 1.5 min per spot, for 10 spots. In repeated CB-PDT, treatments were performed in 4-day intervals. Daily IOP measurements were recorded. Histological studies were performed at selected time points. An IOP reduction, more sustained following repeated treatments, was detected in all treated eyes but not in fellow eyes or in the control group. On the average, the IOP was restored to pretreatment levels 4 days after the last treatment. No serious adverse events were observed and the CB architecture was intact at the end of the experiment. Repeated CB-PDT is safe and results in a short-term reduction of IOP. Induced CB alterations are reversible.

Evaluation of potential retinal toxicity of adalimumab (Humira).

PURPOSE: The purpose of this study is to evaluate the retinal toxicity of two doses of adalimumab (Humira), a recombinant human IgG1 monoclonal antibody specific for human tumor necrosis factor (TNF), when injected intravitreally in rabbits. METHODS: Sixteen male pigmented rabbits (divided into two groups, eight animals per group) were used for this study. Two concentrations of adalimumab were tested: 0.5 mg/0.1 ml and 5 mg/0.1 ml. Each concentration was injected intravitreally randomly in one eye (study group) of each rabbit (group I received 0.5 mg/0.1 ml and group II received 5.0 mg/0.1 ml), while in the other eye (control group) 0.1 ml of sterile balanced saline solution (BSS) was injected. Slit-lamp and funduscopic examinations were performed every second day for 2 weeks for signs of infection, inflammation and toxicity. A baseline electroretinogram (ERG) was performed before the experiment and at the last follow-up day (day 14). ERG examination followed ISCEV standards. At the last follow-up day, the animals were sacrificed and the enucleated eyes were prepared for histological evaluation of retinal toxicity. RESULTS: No differences in ERG responses at photopic and scotopic conditions were observed in eyes injected with either concentration of adalimumab or BSS. Furthermore, histologic examination of the retina in the enucleated eyes (in all groups) did not demonstrate any evidence of drug toxicity. CONCLUSIONS: Intravitreal adalimumab did not appear toxic to the retina in this experimental model at concentrations of 0.5 and 5 mg. If found safe in additional studies, intravitreally injected adalimumab could be evaluated for efficacy in the treatment of inflammatory eye conditions.

Tono-Pen XL tonometry during application of a suction ring in rabbits.

BACKGROUND: The purpose of this study is to evaluate the use of Tono-Pen XL in measuring IOP during the application of a suction ring in rabbit eyes with manometrically controlled IOP. METHODS: Tono-Pen XL was calibrated against direct manometry in 10 rabbit eyes. A suction ring was then applied in 4 rabbit eyes and the IOP was determined manometrically during suction ring application at 350 mmHg vacuum pressure. Finally, in 6 catheterized rabbit eyes the IOP was measured with Tono-Pen XL during suction ring application at suction vacuum from 350 to 650 mmHg, while keeping actual IOP stable at 30 mmHg and 60 mmHg. RESULTS: Linear regression analysis revealed that the Tono-pen XL was reliable for IOPs between 10 and 70 mmHg (R2 = 0.9855). Direct manometry during suction ring application showed no statistically significant variation of Tono-Pen XL readings when the incanulation manometry intraocular pressure changed from 30 mmHg to 60 mmHg and no statistically significant correlation between suction vacuum and IOP measurements. CONCLUSION: Tono-Pen XL measurements are unreliable during the application of a suction ring on living rabbit eyes even when the actual IOP is forced to be within the validated range of Tono-Pen XL measurements. This inaccuracy is probably related to altered corneal and scleral geometry and stress.

Ocular rigidity evaluation after photorefractive keratectomy: an experimental study.

PURPOSE: To evaluate possible changes of the ocular rigidity coefficient in vivo after photorefractive keratectomy (PRK) in a series of rabbit eyes, using an invasive ocular rigidity measurement device. METHODS: Sixteen eyes of 8 rabbits were used in this study. One eye from each rabbit underwent PRK for -10.00 diopters (D) in a 5-mm optical zone (92 microm) while the fellow eye served as the control. Five weeks later, the rabbits were examined under general anesthesia. The pressure-volume relationship and the ocular rigidity coefficient were determined in all 16 eyes, by injecting 200 microL of saline solution (in increments of 4.5 microL) through the limbus into the anterior chamber, while the intraocular pressure (IOP) was continually monitored with a transducer, up to a maximum limit of 40 mmHg. Data within an IOP range of 10 to 40 mmHg were used to calculate the ocular rigidity coefficient. RESULTS: The preoperative central corneal thickness was comparable (P = .73, paired t test) in the pre-PRK eyes (mean: 347.5 +/- 17.11 microm) and control eyes (mean: 349.1 +/- 17.46 microm). No statistically significant difference was noted in measured ocular rigidity coefficient between eyes treated with PRK and control eyes (mean rigidity coefficient: 0.42 +/- 0.12 mmHg/microL [range: 0.23 to 0.56] and 0.47 +/- 0.12 mmHg/microL [range: 0.28 to 0.62], respectively, with 95% confidence interval of the difference, lower: -0.10 to upper: 0.015, P = .121). CONCLUSIONS: Photorefractive keratectomy did not significantly alter ocular rigidity measurements in this experimental model.

The use of intravitreal etanercept in diabetic macular oedema.

The aim of this pilot study was to investigate the effect of intravitreal administration of etanercept in refractory diabetic macular edema. Seven patients diagnosed with diabetic macular edema, refractory to previous treatment, were enrolled. They all received 2 consecutive intravitreal injections of 2.5 mg (0, 1 ml) of Etanercept (Enbrel), with a two-week interval. In all patients visual acuity assessment, fundoscopy and fluorescein angiography were performed prior to the first injection, weekly for the first month, as well as 2 and 3 months following the first injection. No adverse reactions or adverse events were noticed in any patient. Analysis of the data indicates a trend for improvement of visual acuity, a slight worsening of hard exudates and fluorescein leakage, while hemorrhages remained stable, 3 months after initiation of therapy. However, no statistical significance has been reached. This small pilot study did not reveal any improvement in the clinical course of patients with refractory diabetic macular edema after the intravitreal injection of etanercept. Further research is warranted in order to obtain conclusive results concerning the role of anti-TNF therapy in diabetic macular edema.

One-year results of photorefractive keratectomy and laser in situ keratomileusis for myopia using a 213 nm wavelength solid-state laser.

PURPOSE: To study the long-term results of photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) in low to moderate myopic corrections using the Pulzar Z1 system (CustomVis), a 213 nm wavelength solid-state laser. SETTING: University refractive surgery center. METHODS: This prospective noncomparative case series comprised 20 patients (40 eyes) who had refractive surgery using the Pulzar Z1 laser system. Manifest refraction, uncorrected visual acuity, best spectacle-corrected visual acuity (BSCVA), safety, predictability, stability, and confocal microscopy images were evaluated. RESULTS: Ten patients (20 eyes) had PRK and 10 patients (20 eyes) had LASIK. The mean follow-up was 13.9 months +/- 1.1 (SD) (range 12 to 17 months) and 14.6 +/- 1.2 months (range 12 to 18 months) in the PRK group and LASIK group, respectively. No eye lost a line of Snellen BSCVA during the follow-up period; 2 eyes (10%) gained 2 Snellen lines. There was a statistically significant decrease in spherical equivalent manifest refraction postoperatively in both groups (P<.05). Refractive stability was obtained during the first postoperative month and remained stable during the follow-up period, with no significant changes between any interval in both groups (P>.05). At the last follow-up, 95% of all eyes were within +/-1.00 diopter of emmetropia. No late postoperative complications were observed. CONCLUSION: Refractive surgery using the Pulzar Z1 213 nm wavelength solid-state laser was a safe, effective procedure in the treatment of low to moderate myopia.

Spontaneous closure of macular holes developed after pars plana vitrectomy.

PURPOSE: To report a small, retrospective, noncomparative case series (3 patients) of idiopathic macular holes with spontaneous closure in previously vitrectomized eyes. METHODS: The first patient developed a macular hole 14 months after vitrectomy for penetrating ocular trauma. In the rest of the patients, the macular holes were documented ten days and two months after vitrectomies for retinal detachment. RESULTS: In all cases the macular holes resolved spontaneously 2 years, 6 and 9 months after their documentation, respectively. CONCLUSIONS: Despite the limitations placed by the small sample of studied patients, it seems that spontaneous closure of macular holes developed after vitrectomy can happen as part of their natural course. Both pathogenetic and repair factors involved in macular hole can act spontaneously in a vitrectomized eye.

Contact transscleral ciliary body photodynamic therapy in pigmented rabbits using verteporfin and diode laser: evaluation of treatment parameters.

PURPOSE: To evaluate the treatment parameters necessary for achieving ciliary body photodynamic damage, enough to significantly reduce IOP, using verteporfin and a diode laser. DESIGN: Animal study. METHODS: The right eye ciliary body of 30 pigmented rabbits was irradiated using verteporfin (Visudyne) and a diode laser. Photosensitizer dose ranged from 0.375 to 2 mg/kg. Three adjacent laser spots were applied 0.5 mm behind limbus at 12 o'clock position using a contact transscleral technique. The laser power was ranging from 10 to 70 mW and the duration of irradiation from 1 to 5 min per spot. The left eyes of the rabbits were used as controls. Animals were sacrificed 24 hours after the procedure and their eyes were evaluated by means of light and electron microscopy. A step-by-step approach was adopted with adjustment of experimental parameters according to histological findings. The end point was to identify the irradiation parameters necessary for induction of photodynamic damage while minimizing thermal damage. Subsequently, 10 more animals were used in order to verify the effectiveness of these irradiation parameters in reducing the intraocular pressure. RESULTS: The therapy parameters that led to photodynamic effect avoiding thermal damage were laser power of 25 mW, irradiation time of 3 min per spot, and verteporfin dose of 1 mg/kg. Transscleral ciliary body irradiation using these parameters resulted in vascular thrombosis of ciliary vessels and in substantial edema, resulting in separation of the two ciliary epithelium layers. These parameters were applied to 4 rabbits, resulting in a mean IOP reduction of 1.8 mmHg +/- 1.2 that lasted for 4 days. An increase of the laser power to 35 mW tested in 6 additional animals, resulted in mean IOP reduction of 2.2 mmHg +/- 1.2, lasting 6 days; some minimal thermal damage was seen with the later settings. CONCLUSION: The combination of verteporfin and 690 nm diode laser is effective for the induction of ciliary body photodynamic damage, which results in significant but temporary IOP reduction, after transscleral PDT in pigmented rabbits. With appropriate parameter selection, intraocular pressure reduction can be achieved while thermal damage is kept to a minimum.