Long-term results of the effect of intravitreal ranibizumab on the retinal arteriolar diameter in patients with neovascular age-related macular degeneration.

PURPOSE: To study the effect of intravitreal (IVT) ranibizumab on the retinal arteriolar diameter in patients with neovascular age-related macular degeneration (AMD). METHODS: Ten eyes of 10 patients with previously untreated neovascular AMD were included. All eyes had three monthly IVT injections of ranibizumab and then were retreated as needed, based on visual acuity and optical coherence tomography (OCT) criteria. The diameter of the retinal arterioles was measured in vivo with a retinal vessel analyser (RVA) before the first IVT injection, 7 and 30 days after the first, the second and the third injection, and at month 12 of follow-up. RESULTS: A significant vasoconstriction of the retinal arterioles was observed following each one of the first three IVT injections of ranibizumab. Thirty days following the first, second and third injection, there was a mean decrease of 8.4 ± 3.2%, 11.9 ± 4.5% and 18.5 ± 7.2%, respectively, of the retinal arteriolar diameter compared with baseline (p < 0.01). At month 12, the vasoconstriction was still present with a mean decrease of 19.1 ± 8.3% of the retinal arteriolar diameter compared with baseline (p < 0.01). Median number of ranibizumab injections was 4 (range 3-10). There was no correlation between the number of injections and percentage diameter decrease at month 12 (r = -0.54, p > 0.1). There was no significant change in mean arterial pressure (MAP) during the period of follow-up (p > 0.05). CONCLUSIONS: These results suggest that IVT ranibizumab induces sustained retinal arteriolar vasoconstriction in eyes with neovascular AMD.

Experimental application of tissue adhesives in corneal traumas.

OBJECTIVE: To evaluate intraoperative difficulties of the use of glues for corneal trauma.
 METHODS: Partial or full-thickness perpendicular corneal incisions (3-4 mm straight cuts) near the limbus (perpendicular or parallel to it) were made in 8 albino rabbits and were then sealed with fibrin or cyanoacrylate glue. Follow-up examinations were performed under the surgical microscope. Tissue specimens were also taken for light microscopic evaluation. 
 RESULTS: The cyanoacrylate glue polymerized almost immediately after application on the tissue, limiting the ability of the surgeon to oppose the corneal incisions appropriately. The fibrin glue polymerized more gradually, giving enough time for manipulations to reconstruct the wound properly and for removal of excessive glue, especially when the 2 components were applied separately. Excessive glue and crust formation on the eye surface induced irritation.
 CONCLUSIONS: Fibrin glue for the reconstruction of corneal wounds was easier to use than cyanoacrylate glue and caused less glue crust formation on the corneal surface. The speed of polymerization is an important factor. Excessive glue on the cornea was irritating.

Retinal vessel diameter can reliably be determined in minipigs using Retinal Vessel Analyser with a microscope-mounted fundus camera.

PURPOSE: Retinal Vessel Analyser (RVA) is a validated instrument to measure retinal vessel diameter in humans. The purpose of this study was to assess the reproducibility (inter-observer reliability) and the repeatability (test-retest reliability) of RVA with a microscope-mounted fundus camera to determine retinal vessel diameter in minipigs. METHODS: Ocular fundus image from five anaesthetized minipigs was recorded in a digital videotape for approximately 5 min, under stable systemic arterial pressure and gas conditions. To evaluate the reproducibility, each one of two investigators used RVA to measure the diameter of the superior temporal retinal artery on five separate 30-second video sequences from each minipig, which were the same video sequences for both investigators. To evaluate the repeatability, one investigator performed five measurements on a single, randomly selected, 30-second video sequence from each minipig. The reproducibility was determined using the intra-class correlation coefficient (ICC), and the repeatability was assessed using the coefficient of variation (COV). Bland-Altman plots were also used to assess agreement between the two investigators. RESULTS: Retinal arteriolar diameter measurements with RVA in minipigs were highly reproducible. Differences between the two investigators were lower than 0.7%. The ICC was 1.00, indicating perfect reproducibility, and the mean COV was 0.18%, reflecting excellent repeatability of the measurements with RVA. CONCLUSION: Retinal vessel diameter can reliably be determined not only in humans, but also in minipigs, using the commercially available RVA apparatus and a microscope-mounted fundus camera.

Vasomotor effect of intravitreal juxta-arteriolar injection of L-lactate on the retinal arterioles after acute branch retinal vein occlusion in minipigs.

PURPOSE: To investigate the effect of L-lactate on retinal arteriolar diameter after acute branch retinal vein occlusion (BRVO) in minipigs. METHODS: Thirteen eyes of 13 minipigs were evaluated, with the animals under general anesthesia. BRVO was induced by a standard method of argon laser endophotocoagulation. Two hours after BRVO, an intravitreal, juxta-arteriolar microinjection of 50 µL L-lactate 0.5 M (pH 7.4) was performed in nine eyes. Four eyes received a microinjection of 50 µL of the solvent (pH 7.4) that was used to prepare the solution of L-lactate and served as controls. Retinal arteriolar diameter changes were measured using a retinal vessel analyzer. RESULTS: Overall (n = 13), 2 hours after BRVO, there was a 9.0% ± 1.4% decrease in the retinal arteriolar diameter in the affected ares compared to baseline (P < 0.001). An increase of 26.2% ± 8.2% (P = 0.004) of the arteriolar diameter was evidenced 5 minutes after L-lactate juxta-arteriolar microinjection (n = 9) compared with the diameter before L-lactate microinjection. Thereafter, the vasodilatory effect of L-lactate persisted and remained significant until the end of the study period (27.7% ± 7.8% at 30 minutes) compared with the diameter before L-lactate microinjection (P = 0.002). Microinjection of the solvent alone (n = 4) did not produce any significant effect on the retinal arterioles, which remained constricted at all time-points (P > 0.1). CONCLUSIONS: These findings demonstrate a significant arteriolar vasodilation after intravitreal juxta-arteriolar L-lactate microinjection in eyes with experimental BRVO in the affected areas. L-lactate microinjection can reverse the arteriolar vasoconstriction that occurs in acute experimental BRVO.

Pars plana vitrectomy in the treatment of severe complicated toxoplasmic retinochoroiditis.

PURPOSE: To present the anatomic and functional results of pars plana vitrectomy performed in severe complicated toxoplasmic retinochoroiditis. METHODS: Three patients, 2 women and 1 man aged 57, 22, and 57 years, are presented. The first patient was under immunosuppressive therapy for dermatomyositis and underwent diagnostic/therapeutic vitrectomy for severe toxoplasmic panuveitis with dense vitritis. The other 2 patients underwent vitrectomy for macula-off rhegmatogenous retinal detachment that developed after severe toxoplasmic panuveitis. RESULT: Preoperative visual acuity was hand movement for the first 2 patients and 20/400 for the third. All patients received pars plana vitrectomy with epiretinal membrane peeling, laser photocoagulation, and SF6 gas tamponade. The second and third patients needed 5 and 3 additional operations, respectively, including extensive retinotomies and silicone-oil tamponade, for recurrent retinal detachment due to proliferative vitreoretinopathy. At the end of the follow-up period (11, 5, and 1 year, respectively), the retina was attached and visual acuity was 20/30 for the first patient but counting fingers for the other 2 patients. CONCLUSIONS: Severe panuveitis and/or recurrent retinal detachment may develop in some cases of ocular toxoplasmosis, compromising the visual prognosis. Retinal detachment due to toxoplasmosis is generally complex, and long-acting tamponade with silicone oil should be contemplated for anatomic retinal reattachment.

Corneal infiltrates after corneal collagen cross-linking.

PURPOSE: To present a case of advancing keratoconus treated with corneal collagen cross-linking (CXL) with ultraviolet A (UVA) light and riboflavin complicated with sterile infiltrates. METHODS: The patient's cornea was de-epithelialized and CXL was performed with application of riboflavin and exposure to UVA light (370 nm, 3 mW/cm2) for 30 minutes. RESULTS: Early in the postoperative period, the patient presented with 11 deep stromal infiltrates of 1 to 2 mm with clear demarked edges in a circle near the limbus with some clear cornea. Corneal cultures were negative. Treatment consisted of antibiotic ofloxacin and tobramycin four times daily, and dexamethasone drops six times daily. After 2 months, scars remained evident. CONCLUSIONS: This complication has not been reported previously and may be an individual hypersensitivity reaction to the riboflavin or UVA light in the anterior stroma.

Retinal vessel analyzer measurements of the effect of panretinal photocoagulation on the retinal arteriolar diameter in diabetic retinopathy.

PURPOSE: The purpose of this study was to investigate the effect of panretinal photocoagulation (PRP) on the retinal arteriolar diameter in patients with diabetic retinopathy using a retinal vessel analyzer. METHODS: Ten eyes of 6 consecutive patients with type II diabetes and severe nonproliferative or proliferative diabetic retinopathy were studied prospectively. Measurements of the retinal arteriolar diameter were performed before the first photocoagulation session and after the end of the PRP treatment. RESULTS: Retinal arteriolar diameter before PRP was 131 +/- 15 arbitrary units and decreased to 112 +/- 14 arbitrary units after PRP (P = 0.012). There was a significant vasoconstriction of 13.8% +/- 8.3% following PRP. Mean visual acuity before and after PRP was 0.31 +/- 0.36 logarithm of the minimal angle of resolution and 0.28 +/- 0.30 logarithm of the minimal angle of resolution, respectively (P = 0.68). There was no significant change in mean arterial pressure before and after PRP (P = 0.89). There was no correlation between the visual acuity change or the number of laser burns and the percentage change in the retinal arteriolar diameter (P > 0.1). CONCLUSION: Panretinal photocoagulation has a vasoconstrictive effect on retinal arterioles in patients with severe nonproliferative or proliferative diabetic retinopathy. These results are consistent with an autoregulatory response of the retinal circulation to increased inner retinal oxygen tension after PRP. The retinal vessel analyzer is a fast, accurate, noninvasive, online measuring system for the study of the retinal vascular response to PRP in patients with diabetic retinopathy.

Intravitreal ranibizumab may induce retinal arteriolar vasoconstriction in patients with neovascular age-related macular degeneration.

OBJECTIVE: To study the effect of intravitreal (IVT) ranibizumab (Lucentis; Genentech, Inc, San Francisco, CA) on the retinal arteriolar diameter in patients with neovascular age-related macular degeneration (AMD). DESIGN: Prospective consecutive interventional case series. PARTICIPANTS: Eleven eyes of eleven patients with previously untreated neovascular AMD. METHODS: All eyes had 3 monthly IVT injections of ranibizumab. The diameter of the retinal arterioles was measured in vivo with a retinal vessel analyzer (RVA) before the first IVT injection and then 7 and 30 days after the first, second, and third injections. MAIN OUTCOME MEASURES: Primary end points were changes in retinal arteriolar diameter and mean arterial pressure (MAP) after IVT ranibizumab. Secondary end points were changes in best-corrected visual acuity (BCVA), central retinal thickness, and intraocular pressure after IVT ranibizumab, and appearance of adverse events during the follow-up period. RESULTS: A significant decrease of the retinal arteriolar diameter was observed after each IVT injection of ranibizumab. Thirty days after the first, second, and third injections, there was a mean decrease of 8.1+/-3.2%, 11.5+/-4.4%, and 17.6+/-7.4%, respectively, of the retinal arteriolar diameter compared with baseline values (P<0.01). There was no significant change in MAP during the period of follow-up (P>0.05). Thirty days after the third IVT injection of ranibizumab, mean BCVA improved by 6.5+/-4.9 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, and central retinal thickness decreased by 91+/-122 microm (P = 0.03). CONCLUSIONS: These results suggest that IVT ranibizumab may induce retinal arteriolar vasoconstriction in patients with neovascular AMD after IVT ranibizumab. Further studies evaluating larger sample sizes are needed to confirm these results and potential adverse effects on the retinal circulation in patients with AMD and retinal vascular diseases. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Lactate-induced retinal arteriolar vasodilation implicates neuronal nitric oxide synthesis in minipigs.

PURPOSE: To investigate the role of neuronal nitric oxide (NO) synthesis in the retinal vasodilatory response to lactate in minipigs. METHODS: Thirteen eyes of 13 minipigs were evaluated. Ten eyes received an intravenous infusion of N(omega)-nitro-L-arginine methyl ester (L-NAME). After 1 hour, the same eyes received an intravitreous juxta-arteriolar microinjection of 30 microL of L-lactate 0.5 M (pH 7.4) through a micropipette. Ten minutes later, 9 of 10 eyes received an intravitreous juxta-arteriolar microinjection of 30 microL of L-NAME 0.01 M (pH 7.4), and 1 received physiologic saline solution (PSS). The remaining three eyes received a microinjection of 30 microL of L-lactate 0.5 M (pH 7.4), without intravenous or intravitreous L-NAME. RESULTS: The three eyes that received juxta-arteriolar injection of L-lactate only showed a reproducible increase in retinal arteriolar diameter that persisted during the entire study period (maximum effect at 20 minutes, 40.9% +/- 3.2%). Retinal arteriolar diameter decreased by 4.1% 1 hour after intravenous L-NAME when compared with baseline but the difference did not reach significance. The juxta-arteriolar injection of L-lactate induced a significant increase in retinal arteriolar diameter (22.7% and 28.7% at 5 and 10 minutes, respectively; P < 0.01), followed by a significant decrease (8.6%; P < 0.01) 10 minutes after juxta-arteriolar injection of L-NAME. Injection of PSS had no effect on retinal arteriolar diameter. CONCLUSIONS: Juxta-arteriolar administration of L-lactate induced vasodilation, which was also observed with continuous intravenous infusion of L-NAME. Moreover, juxta-arteriolar L-NAME microinjection significantly suppressed the vasodilatory effect of L-lactate. These data suggest that neuronal-derived NO is an important mediator of lactate-induced vasodilation in minipigs.