Intravitreal thalidomide reduces experimental preretinal neovascularisation without induction of retinal toxicity.

BACKGROUND/AIMS: Proliferative retinopathies remain the most common causes of blindness. Retinal neovascularisation is induced by hypoxic upregulation of angiogenic growth factors, such as vascular endothelial growth factor (VEGF). Thalidomide has been shown to be anti-angiogenic via reduction of VEGF levels. We investigated the effect of intravitreal application of thalidomide on neovascularisation and retinal toxicity in a mouse model of proliferative retinopathy. METHODS: C57BL/6J mice were exposed to 75% oxygen from postnatal day (p) 7 to p12. Immediately after transfer to room air at p12, mice received an intravitreal injection of 150 microg/microl thalidomide or control solution. Preretinal neovascularisation was quantified at p17. VEGF levels were assessed in whole retinal lysates at p13 and p17. Retinal toxicity was assessed by measuring retinal layer thickness and by analysing caspase-3 activity and apoptotic cell counts in retinal layers to examine retinal apoptosis. RESULTS: Intravitreal application of thalidomide significantly reduced preretinal neovascularisation by 62% compared with control treated contralateral eyes (p=0.01). Interestingly, this effect was established without a change in retinal VEGF levels. Intravitreal thalidomide was not toxic, as retinal layer thickness, retinal caspase-3 activity and apoptotic cell counts were unaltered. CONCLUSION: These data indicate that intravitreal application of thalidomide can be an effective and safe way to treat retinal neovascularisation.

Intraocular concentration of triamcinolone acetonide after intravitreal injection in the rabbit eye.

PURPOSE: To examine the decrease in the intraocular concentration of intravitreally injected triamcinolone acetonide over an 8-month period in a rabbit model. DESIGN: Experimental study. PARTICIPANTS: The study included 18 white New Zealand rabbits. METHODS: The animals received an intravitreal injection of 6 mg triamcinolone acetonide. Vitreous and aqueous humor samples of the anterior and posterior chamber were taken at the first and third day, at 1 and 2 weeks, and at 1, 1.5, 2, 3, 6, and 8 months. The concentrations of triamcinolone were analyzed using a high-phase liquid chromatography assay. MAIN OUTCOME MEASURES: Intraocular concentration of triamcinolone during follow-up. RESULTS: Over the entire study period, triamcinolone concentrations were significantly higher in the vitreous samples than in the anterior chamber samples (day 1, 14 434+/-10 768 microg/l vs. 21.0+/-18.9 microg/l; day 30, 571.3+/-329.6 microg/l vs. 6.1+/-1.6 microg/l; month 8, 70.7+/-37.0 microg/l vs. 3.3+/-1.6 microg/l). In the anterior chamber, the triamcinolone concentrations were highest at 3 days after the injection (28.9+/-24.5 microg/l), and in the vitreous, the concentrations were highest at the first day (14,434.0+/-10,768 microg/l). Triamcinolone levels in the vitreous and in the anterior chamber followed a 2-compartment model, with an exponential decrease in the concentration within the first 4 weeks, followed by a steady decline over the following months. At 8 months, the triamcinolone concentrations were 70.7+/-37.0 microg/l in the vitreous samples and 3.3+/-1.6 microg/l in the anterior chamber samples. CONCLUSIONS: The decrease in the concentration of triamcinolone after an intravitreal injection of 6 mg in rabbits follows a 2-compartment model, with an exponential decrease in the first 4 weeks followed by a more linear decrease. During the entire study period, the triamcinolone concentration was significantly higher in the vitreous than in the anterior chamber. After a single intravitreal triamcinolone injection of 6 mg in rabbits, triamcinolone is detectable for at least 8 months after the injection.

Visual acuity change after intravitreal triamcinolone in various types of exudative age-related macular degeneration.

OBJECTIVE: The aim of this study was to compare the visual acuity change after an intravitreal high-dose injection of triamcinolone acetonide (TA) in various types of exudative age-related macular degeneration (AMD). PARTICIPANTS: The interventional comparative case series study included 142 patients (146 eyes) with progressive exudative AMD differentiated into the occult type (n = 78; 53.4%), minimal classic type (n = 45; 30.8%), predominantly classic type (n = 17; 11.6%), and the purely classic type (n = 6; 4.1%). Mean follow-up was 9.7 +/- 7.0 months (3-35.7 months). METHODS: Single intravitreal injection of approximately 20 mg of TA. OUTCOME MEASURES: Visual acuity, intraocular pressure (IOP). RESULTS: Gain in visual acuity measured at 1 month (P = 0.20), 2 months (P = 0.43), and at 3 months (P = 0.38) after the intravitreal injection of triamcinolone and maximal gain in visual acuity during the whole follow-up (P = 0.81) did not vary significantly between the 4 study groups. Correspondingly, the size of a retinal pigment epithelium detachment was not significantly associated with the change in visual acuity at 1 month (P = 0.62), 2 months (P = 0.24), 3 months (P = 0.96), or the maximal gain in visual acuity during follow-up (P = 0.93). The amount of rise in IOP, compared with the baseline value (6.5 +/- 7.4 mmHg), was statistically not associated with the type of subfoveal membrane (P = 0.20; 95% confidence interval: -0.52, 2.45). CONCLUSIONS: The change in visual acuity and the rise in IOP in patients with exudative AMD receiving an intravitreal triamcinolone monotherapy is statistically independent of the type of subfoveal membrane, including the size of a retinal epithelium detachment.

Repeated intravitreal injection of triamcinolone for exudative age-related macular degeneration.

BACKGROUND: Intravitreal triamcinolone acetonide has been discussed as treatment for exudative age-related macular degeneration (AMD). OBJECTIVES: To give an updated report on repeated intravitreal injections of triamcinolone acetonide (IVTA) for the treatment of exudative AMD. METHODS: The case-series study included 24 patients (24 eyes) with progressive exudative AMD who had shown an increase in, or stabilization of, visual acuity after a first IVTA, and who eventually experienced a deterioration of visual acuity. The 24 (6.5%) eyes were selected out of a total group of 369 eyes who had received IVTA for exudative AMD within the last 5 years. All patients of the study received a second IVTA (approximately 20 mg) 3.7-38.5 months after the first injection. Main outcome measure was visual acuity. RESULTS: After the first injection, best corrected visual acuity improved significantly (p = 0.001) from 0.75 +/- 0.34 logMAR to a minimum of 0.58 +/- 0.30 logMAR during follow-up, with 10 (42%) eyes improving in visual acuity by two or more Snellen lines. Towards the end of follow-up after the first injection, best corrected visual acuity decreased significantly (p = 0.03) compared with the baseline value. After the second injection, visual acuity did not change markedly from baseline to a mean maximal visual acuity during follow-up. Comparing the last postoperative examination at the end of the follow-up after the second IVTA with the preoperative examination, a significantly (p = 0.001) higher number of eyes lost in visual acuity [19 (79%) eyes] than gained in visual acuity [3 (12%) eyes]. CONCLUSIONS: In selected eyes with an increase in visual acuity after a first IVTA (20 mg), repeated IVTA temporarily stabilizes visual acuity with a drop in visual acuity towards the end of follow-up.

Further investigation of the tolerance and mechanical adjustability of the *Acri.Tec AR-1 PC/IOL in rabbit eyes: an intraocular lens with reversibly adjustable optical power.

PURPOSE: To examine the tolerance and mechanical function of an adjustable intraocular lens (IOL) in rabbit eyes. METHODS: Implantation of the *Acri.Tec AR-1 PC/IOL into 14 rabbit eyes. Manipulation of the lens 8 weeks after implantation in order to change the refractive power. Follow-up for up to 5 months. Histopathologic examination of the eyes. RESULTS: Implantation and mechanical adjustment of the PC/IOL were possible. Eyes healed normally. No difference between eyes containing the *Acri.Tec AR-1 PC/IOL and eyes containing the control PC/IOL could be detected with respect to signs of inflammatory reaction, corneal transparency, intraocular pressure and histopathologic appearance. Histopathologic examination of the eyes showed that the *Acri.Tec AR-1 PC/IOL did not cause any damage in rabbit eyes. CONCLUSION: The *Acri.Tec AR-1 PC/IOL is well tolerated in rabbit eyes for extended periods of time, suggesting that this PC/IOL should be well tolerated in the long run. Surgical adjustment of the adjusting element can be performed with little effort several weeks after implantation.

Triamcinolone acetonide-induced ocular hypertension.

PURPOSE: The aim of this study is to report on the clinical course of a patient showing markedly increased intraocular pressure (IOP) caused by intravitreal triamcinolone acetonide. METHODS: A 33-year-old patient received an intravitreal injection of approximately 20 mg of triamcinolone acetonide (TA) as treatment of otherwise therapy-resistant uveitis. She experienced an IOP rise to values over 40 mmHg for a period for more than 3 months, despite maximal antiglaucomatous medical therapy. Peak IOP was 55 mmHg. RESULTS: Neither confocal scanning laser tomography nor qualitative assessment of optic disc photographs nor perimetry showed development of glaucomatous changes. Scanning laser polarimetry of the retinal nerve fiber layer suggested a slight loss in the nasal upper fundus quadrant. CONCLUSIONS: Relatively young patients with a pronounced TA-induced rise in IOP, unresponsive to maximal antiglaucomatous medication, may not necessarily undergo antiglaucomatous surgery if the rise in IOP does not last longer than approximately 3 months.

Duration of the effect of intravitreal triamcinolone acetonide in eyes with exudative age-related macular degeneration.

OBJECTIVE: The aim of this study was to evaluate the duration of the effect of an intravitreal injection of approximately 20 mg of triamcinolone acetonide (TA) on visual acuity and intraocular pressure (IOP) in patients with exudative age-related macular degeneration (AMD) with subfoveal choroidal neovascularization. PARTICIPANTS: The prospective, clinical, interventional, case series study included 69 patients (71 eyes) with exudative AMD who showed an increase in visual acuity by at least 2 Snellen lines after an intravitreal injection of approximately 20 mg TA. Mean follow-up was 11.5 +/- 7.4 months (3.3-35.7 months). The main outcome measure was visual acuity. RESULTS: Within the first week after the injection, visual acuity and IOP started to increase significantly (P < 0.001) by reaching a plateau-like maximum at 1-6 months after the injection. Visual acuity and IOP returned to baseline values 7-9 months after the injection. Increase of IOP was statistically (P = 0.72) independent of the change in visual acuity. CONCLUSIONS: In patients with exudative AMD, who have shown an increase of at least 2 Snellen lines in visual acuity, the effect of intravitreal TA (dosage approximately 20 mg) lasts 7-9 months with respect to an increase in visual acuity and IOP.

Intravitreal triamcinolone acetonide for diabetic macular edema: a prospective, randomized study.

PURPOSE: The aim of this study was to examine the visual outcome of patients receiving an intravitreal injection of triamcinolone acetonide (TA) as treatment of diffuse diabetic macular edema (DDME). METHODS: This prospective, placebo-controlled, randomized, clinical interventional study included 40 eyes (38 patients) with DDME, with 28 (70%) eyes randomized to treatment and 12 (30%) eyes randomized to receive a placebo injection. Thirty-six (36) (90%) eyes completed the 3-month study visit, and 32 (80%) eyes completed the 6-month study visit. The treatment group received an intravitreal injection of approximately 20 mg of TA. RESULTS: Visual acuity increased significantly (P < 0.001) in the study group by 3.4 +/- 2.5 Snellen lines. In the control group, visual acuity did not change significantly (P = 0.07) during follow-up. Difference in change of best visual acuity was significant (P < 0.001) between both groups. At 3 months after baseline, 11 (11/26; 42%) eyes and 10 (10/26; 39%) eyes, respectively, improved by at least 2 and 3 lines, respectively, in the study group, versus 2 (2/10; 20%) eyes and 1 (1/10; 10%) eye in the control group. At 6 months after baseline, 11 (11/23; 48%) eyes and 9 (9/23; 39%) eyes, respectively, improved by at least 2 and 3 lines, respectively, in the study group, versus 0 (0%) eyes and 0 (0%) eyes in the control group. The difference was significant for the 2-line improvement (P = 0.01) and 3-line improvement (P = 0.03). CONCLUSIONS: Using a dosage of approximately 20 mg of intravitreal TA, visual acuity temporarily increases for 6 months after injection.

Optical coherence tomography of the optic nerve head: interindividual reproducibility.

PURPOSE: Optical coherence tomography may be a new technique for quantitative 3-dimensional assessment of the optic nerve head for diagnosis of optic nerve anomalies and diseases such as the glaucomas. The purpose of the present study was to examine its reproducibility. PATIENTS AND METHODS: The clinical noninterventional study included 10 randomly chosen eyes of 10 healthy individuals who underwent 24 optical coherence tomographic examinations with the high-resolution and fast scan program, interactively corrected or uncorrected. The pupils were not dilated. All examinations were performed by 3 examiners independently of one another. The coefficient of variation was calculated as the ratio of the mean of the standard deviations divided by the mean of the means. RESULTS: The coefficients of variation for redetermination of optic disc area, ranging between 0.047 and 0.119, were lowest for the manually corrected fast scan mode and highest for the uncorrected fast scan mode. For remeasurements of the neuroretinal rim area, the best mean coefficient of variation was 0.073+/-0.026 (corrected fast scan mode). CONCLUSIONS: In healthy eyes, the morphometric measurements of the optic nerve head by optical coherence tomography show a relatively high reproducibility with mean coefficients of variation lower than 10% for remeasurements of the optic disc and neuroretinal rim area. With undilated pupils, reproducibility is better with the fast scan mode with interactive correction of the outlining of the optic disc border than it is with the high-resolution mode.

Repeated intravitreal high-dosage injections of triamcinolone acetonide for diffuse diabetic macular edema.

OBJECTIVE: To report the results of repeated intravitreal injections of triamcinolone acetonide for treatment of diffuse diabetic macular edema. DESIGN: Retrospective interventional comparative study. PARTICIPANTS: The investigation included a study group (the responders) of 19 patients (22 eyes) with diffuse diabetic macular edema, who showed an improvement in visual acuity after an intravitreal injection of approximately 20 mg triamcinolone acetonide, and who received a second intravitreal injection 10.0+/-3.8 months after the first injection. A control group consisted of 31 patients with diffuse diabetic macular edema without treatment during follow-up. METHODS: Intravitreal injection of approximately 20 mg triamcinolone acetonide. MAIN OUTCOME MEASURES: Visual acuity and intraocular pressure. RESULTS: Follow-up after the second injection was 9.1+/-4.9 months. Four patients received a third injection at 9.7+/-3.7 months after the second injection, with a follow-up after the third injection that was at 7.9+/-11.5 months. After the second and third injections, visual acuity increased significantly (P = 0.002 and P = 0.068, respectively) by 1.8+/-2.1 and 4.0+/-2.6 Snellen lines, respectively. Eleven eyes (50%) showed an improvement in visual acuity by at least 2 Snellen lines after the second injection, and 3 patients (75%) experienced a gain in visual acuity by at least 2 Snellen lines after the third injection. Intraocular pressure increased significantly (P<0.01) after each injection, and returned to baseline values before each reinjection. Visual acuity improvement (P>0.05) and intraocular pressure rise did not differ significantly (P>0.55) between the various injections. Improvement in visual acuity and rise of intraocular pressure lasted approximately 6 to 8 months after each injection. CONCLUSIONS: Intravitreal injection of approximately 20 mg triamcinolone acetonide may repeatedly lead to an improvement in visual acuity and a rise of intraocular pressure in patients with diffuse diabetic macular edema. The duration of the effect after each injection is approximately 6 to 8 months. Tachyphylaxis in visual acuity or intraocular pressure outcomes were not observed.

Dynamic contour tonometry for intraocular pressure measurement.

PURPOSE: To compare dynamic contour tonometry as a new method for intraocular pressure measurement with Goldmann applanation tonometry. DESIGN: Clinical observational study. METHODS: The study included 176 eyes of 126 subjects (39 eyes with open-angle glaucoma, 137 normal eyes) and consisted of 528 dynamic contour measurements and 352 Goldmann tonometry measurements. Corneal pachymetry measurements were additionally performed. RESULTS: Mean dynamic contour tonometric measurements (18.71 +/- 5.90 mm Hg) were significantly (P < .001) higher than mean applanation tonometric values (16.98 +/- 5.86 mm Hg), correlating significantly with each other (r(2) = .905, P < .001). The slope of the regression line was 0.95. Correlation with central corneal thickness was significant for applanation tonometry (P = .036), while dynamic contour tonometry was statistically independent of corneal thickness (P = .32). CONCLUSIONS: For measurement of intraocular pressure, dynamic contour tonometry may offer a new technology, which, compared with applanation tonometry, may show a lower dependence on central corneal thickness.

Intereye difference in exudative age-related macular degeneration with minimally classic or occult subfoveal neovascularization after unilateral intravitreal injection of triamcinolone acetonide.

PURPOSE: To report on visual outcome after intravitreal injection of triamcinolone acetonide for exudative age-related macular degeneration. DESIGN: Interventional comparative non-randomized clinical trial. SETTING: Institutional. PATIENTS: Twenty consecutive patients with bilateral exudative age-related macular degeneration with minimally classic or occult subfoveal neovascularisation. INTERVENTIONS: Unilateral intravitreal injection of about 20 mg triamcinolone acetonide into the eye (study group) more severely affected or showing more pronounced progression of the disease. Mean follow-up was 13.5 +/- 4.1 months. MAIN OUTCOME MEASURES: Visual acuity. RESULTS: In the study group, visual acuity increased significantly (P < 0.001) from 0.96 +/- 0.32 logMar to a mean maximum of 0.76 +/- 0.30 logMar during follow-up. An increase in best visual acuity during follow-up was found in 18 (90%) eyes. In 11 (55%) eyes and 7 (35%) eyes, respectively, best visual acuity increased by at least two Snellen lines and three Snellen lines, respectively. In the control group, visual acuity at baseline and the highest visual acuity measurements during follow-up did not vary significantly (P = 0.90). Comparing study group and control group, visual acuity gain was significantly (P = 0.003) higher in the study group. Correspondingly, the number of eyes with an increase in visual acuity (P = 0.002) and with an increase in visual acuity higher > or = 3 lines compared to a loss of > or = 3 lines was significantly (P = 0.027) higher in the study group. CONCLUSIONS: Intravitreal triamcinolone acetonide may temporarily increase visual acuity in eyes with exudative age-related macular degeneration.

Intraocular pressure elevation after intravitreal triamcinolone acetonide injection.

PURPOSE: To report on intraocular pressure (IOP) after intravitreal injections of triamcinolone acetonide. DESIGN: Meta-analysis of previously reported data and case series studies. PARTICIPANTS: The study included 272 patients (305 eyes) receiving an intravitreal injection of approximately 20 mg triamcinolone acetonide as treatment for diffuse diabetic macular edema (n = 84 patients), exudative age-related macular degeneration (n = 181 patients), retinal vein occlusions (n = 20 patients), uveitis (n = 9), pseudophakic cystoid macular edema (n = 6), and other reasons (n = 5). Mean follow-up was 10.4+/-6.7 months (median, 7.9 months; range, 3.0-35.7 months). INTERVENTION: Intravitreal injection of approximately 20 mg triamcinolone acetonide. MAIN OUTCOME MEASURE: Intraocular pressure. RESULTS: Intraocular pressure readings higher than 21 mmHg, 30 mmHg, 35 mmHg, and 40 mmHg, respectively, were measured in 112 (41.2%) patients, 31 (11.4%) patients, 15 (5.5%) patients, and 5 (1.8%) patients, respectively. Triamcinolone-induced IOP elevation was treated by antiglaucoma medication in all but 3 (1.0%) eyes, for which filtering surgery was performed. Mean IOP started to rise 1 week after injection and returned to baseline values approximately 8 to 9 months after injection. Younger age (P = 0.029) was significantly associated with triamcinolone-induced ocular hypertension. Triamcinolone responders and triamcinolone nonresponders did not vary significantly in gender (P = 0.42), refractive error (P = 0.86), diabetes mellitus status (P = 0.74), and reason for treatment. CONCLUSIONS: These findings may be useful for comparing risks and benefits of intravitreal triamcinolone acetonide therapy.

Duration of the effect of intravitreal triamcinolone acetonide as treatment for diffuse diabetic macular edema.

PURPOSE: To evaluate the duration of the effect of intravitreal triamcinolone acetonide on visual acuity in patients with diffuse diabetic macular edema. DESIGN: Clinical interventional case series. METHODS: Subjects were 31 patients (38 eyes) with diffuse diabetic macular edema who received an intravitreal injection of 20- to 25-mg triamcinolone acetonide. Mean follow-up time was 13.2 +/- 6.0 months (6.03-25.2 months). RESULTS: Visual acuity and intraocular pressure began to increase significantly (P =.003) within the first week, reaching a plateaulike maximum at 1 to 7 months postinjection, returning to baseline values 8 to 9 months postinjection. CONCLUSIONS: The effect of an intravitreal injection of approximately 20- to 25-mg triamcinolone acetonide in patients with diffuse diabetic macular edema lasts approximately 7 to 8 months. This information may be helpful in determining the optimal dosage of intravitreal triamcinolone acetonide for the treatment of diffuse diabetic macular edema.

Inter-eye difference in diabetic macular edema after unilateral intravitreal injection of triamcinolone acetonide.

PURPOSE: To report on visual outcome of patients receiving intravitreal triamcinolone acetonide for treatment of diffuse diabetic macular edema. DESIGN: Prospective, comparative clinical interventional study. SETTING: Institutional. patient population: The study included 25 consecutive patients (50 eyes) with bilateral diabetic macular edema. Intervention procedure: Unilateral intravitreal injection of about 20 mg triamcinolone acetonide into the eye (study group) more severely affected by diabetic maculopathy. The contralateral eyes served as control group. Mean follow-up was 7.1 +/- 4.1 months. MAIN OUTCOME MEASURE: Visual acuity, intraocular pressure. RESULTS: In the study group, visual acuity increased significantly (P < or = .001) by 3.0 +/- 2.6 Snellen lines to a peak at two to six months after the injection, and decreased significantly (P = .001) towards the end of follow up. At the end of follow-up, visual acuity was higher, not significantly (P = .18) higher, than at baseline. An increase in visual acuity was found in 23 eyes (92%). In the control group, differences between visual acuity at baseline and at any of the re-examinations during follow-up were not significant (P > .10). In an intra-individual inter-eye comparison, gain in visual acuity was significantly (P < .05) higher in the injected eyes, for the measurements obtained up to four months after injection. CONCLUSIONS: Intravitreal triamcinolone acetonide may temporarily increase visual acuity in eyes with diabetic macular edema.

Intraocular lens with reversibly adjustable optical power: pilot study of concept and safety.

PURPOSE: To evaluate whether it is technically feasible and safe to implant and adjust an intraocular lens (IOL) with reversibly adjustable refractive power designed to correct residual postoperative refractive error. SETTING: Animal study facility, Klinikum Mannheim, University of Heidelberg, Heidelberg, Germany. METHODS: An Acri.Tec AR-1 posterior chamber IOL (PC IOL) was implanted in pig cadaver eyes and in rabbit eyes after the crystalline lens was removed by phacoemulsification. The IOL was manipulated to change the refractive power. The outcome measures were the stability of the IOL during implantation, IOL positioning and rotation, the ability to move the adjustment device after the IOL had been implanted for several weeks, clinical signs of inflammation, and changes in the histopathologic appearance of the eye. RESULTS: Implantation and adjustment of refractive power were possible. The eyes healed normally. There was no difference between eyes with the AR-1 PC IOL and eyes with a control IOL in inflammatory reaction, corneal transparency, or histopathologic appearance. CONCLUSION: The AR-1 PC IOL was easy to implant and well tolerated in rabbit eyes. Surgical adjustment of the adjusting element was performed with little effort several weeks after implantation of the IOL.