Effects of Ranibizumab, Bevacizumab, and Aflibercept on Senescent Retinal Pigment Epithelial Cells

PURPOSE: Anti-vascular endothelial growth factor (VEGF) agents have been used for the last 10 years, but their safety profile, including cytotoxicity against various ocular cells such as retinal pigment epithelial (RPE) cells, remains a serious concern. Safety studies of VEGF agents conducted to date have primarily relied on healthy RPE cells. In this study, we assessed the safety of three anti-VEGF agents, namely, ranibizumab, bevacizumab, and aflibercept, on senescent RPE cells. METHODS: Senescent human induced pluripotent stem cell-derived RPE cells were generated by continuous replication and confirmed with senescence biomarkers. The viability, proliferation, protein expression, and phagocytosis of the senescent RPE cells were characterized 3 days after anti-VEGF treatment with clinical doses of ranibizumab, bevacizumab, or aflibercept. RESULTS: Clinical doses of ranibizumab, bevacizumab, or aflibercept did not decrease the viability or alter proliferation of senescent RPE cells. In addition, the anti-VEGF agents did not induce additional senescence, impair the protein expression of zonula occludens-1 and RPE65, or reduce the phagocytosis capacity of senescent RPE cells. CONCLUSIONS: Clinical dosages of ranibizumab, bevacizumab, or aflibercept do not induce significant cytotoxicity in senescent RPE cells.

Intravitreal injection of anti-vascular endothelial growth factor for patients with various retinal diseases

Vascular endothelial growth factor (VEGF-A) is a major regulator of angiogenesis and vascular permeability. VEGF-A plays an important role in a wide variety of retinal diseases. Therefore, intravitreal injection of anti-VEGF agents is increasingly used for the treatment of various vasoproliferative or exudative retinal diseases. There are several anti-VEGF drugs available that are currently used, but three are most commonly used in practice. They are ranibizumab, bevacizumab, and aflibercept. Ranibizumab is a humanized monoclonal antibody fragment targeting VEGF-A, but bevacizumab, commonly used off-label, is a humanized full-length anti-VEGF antibody. Aflibercept is a recombinant fusion protein consisting of portions of human VEGF receptors 1 and 2 extracellular domains fused to the Fc portion of human IgG1. These anti-VEGF therapies have resulted in unprecedented visual and anatomic outcomes, especially in patients with neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME). Visual stabilization or clinically significant visual improvement can be expected if intravitreal injections of anti-VEGF agents are properly provided for patients with neovascular AMD or DME in the course of the disease. Treating retinal diseases with intravitreal injection of anti-VEGF agents may have potential side effects. Systemic adverse effects attributable to VEGF inhibition may cause thromboembolic events. Acute endophthalmitis is the most feared injection-related ocular side effect. The development of anti-VEGF agents for various retinal diseases provides a safe and effective treatment. There is no doubt that further advances in anti-VEGF therapy can be expected soon.

Posterior Subtenon Triamcinolone Acetonide in Gas-filled Eyes as an Adjunctive Treatment for Complicated Proliferative Diabetic Retinopathy

PURPOSE: To evaluate the effect of adjunctive subtenon injection of triamcinolone acetonide (TA) in gas-filled eyes after vitrectomy for complicated proliferative diabetic retinopathy (PDR). METHODS: This nonrandomized comparative study included 27 patients (27 eyes) who underwent pars plana vitrectomy and gas tamponade for treatment of PDR with tractional or combined tractional-rhegmatogenous retinal detachment and who received subtenon injection of TA (40 mg) at the end of surgery. The study group was compared with the control group (29 eyes), which was matched with the study group for preoperative and intraoperative parameters, but underwent pars plana vitrectomy and gas tamponade without a subtenon injection of TA. RESULTS: Retinal reattachments without reoperation were achieved in 25 eyes (92.6%) and 26 eyes (89.7%) at 6 months (p = 1.000) in the study and control groups, respectively. The study group and the control group did not differ significantly in the frequency of postoperative proliferative vitreoretinopathy, retinal redetachment rate, reoperation rate, macular pucker formation, postoperative vitreous hemorrhage, gain in visual acuity, intraocular pressure, and intraocular inflammation (p > 0.05). CONCLUSIONS: The clinical results of pars plana vitrectomy for complicated PDR are not improved significantly by an adjunctive subtenon TA injection in gas-filled eyes.

Hypertensive Retinopathy and Associated Target Organ Damage in Korean Hypertensive Patients

PURPOSE: To report the relationship between hypertensive retinopathy and associated target organ damage in Korean hypertensive patients. METHODS: A total of 519 hypertensive patients were divided into hypertension retinopathy grades I through IV based on fundus examination. According to the grade of each hypertensive retinopathy, the frequency of target organ damage (cardiovascular disease, chronic kidney disease, and retinal vessel occlusion) and the association with hypertension retinopathy were evaluated. RESULTS: There were 211 patients (40.7%) without hypertensive retinopathy, 226 patients (43.5%) with hypertensive retinopathy grade I, 71 patients (13.7%) with grade II, seven patients (1.3%) with grade III and four patients (0.8%) with grade IV. The numbers of patients with cardiovascular disease were 103 (45.6%) in grade I, 57 (80.3%) in grade II, 3 (42.9%) in grade III, two (50.0%) in grade IV, and 70 (37.4%) in the non-hypertensive retinopathy group. According to four grades, the numbers of patients with cerebrovascular disease were three (1.3%), two (2.8%), zero (0%), and one (25.0%), respectively, with two (0.9%) in the non-hypertensive retinopathy patients. The respective numbers of patients with chronic kidney according to grades I through IV were 14 (6.2%), ten (14.0%), two (28.6%), and four (100.0%), as well as ten (4.7%) in the non-hypertensive retinopathy patients. The respective numbers of patients with retinal vessel occlusion were one (0.4%), two (2.8%), one (14.3%), and one (25.0%), with zero (0%) in the non-hypertensive retinopathy patients. CONCLUSIONS: The significance of hypertensive retinopathy should not be overlooked in Korean hypertensive patients due to an association with various target organ damage.

Clinical Results of Crystalens(R) (AT-45) Accommodating Intraocular Lens

PURPOSE: To evaluate one-year clinical results of Crystalens(R) (AT-45, Eyeonics, CA, USA) accommodating IOL implantation. METHODS: In this retrospective study, 25 eyes of 18 patients had phacoemulsification and Crystalens(R) accommodating IOL implantation. Distance and near visual acuity (VA) during the 12-months were measured. RESULTS: At two months, uncorrected distance visual acuity (VA) of 13 eyes (52.0%) and 21 eyes (84.0%) were 20/25 and 20/40 or better, respectively. At six months, 11 eyes (44.0%) and 21 eyes (84.0%) were 20/25 and 20/40 or better, respectively. At 12 months, 11 eyes (44.0%) and 17 eyes (68.0%) were 20/25 and 20/40 or better, respectively. At two months, the uncorrected near VAs of 11 eyes (44.0%) and 17 eyes (68.0%) were 20/25 and 20/40 or better, respectively. At six months, 9 eyes (36.0%) and 16 eyes (64.0%) were 20/25 and 20/40 or better, respectively. After 12 months, 6 eyes (24.0%) and 16 eyes (64.0%) were 20/25 and 20/40 or better, respectively. CONCLUSIONS: The uncorrected near VAs gradually decreased with the passage of time until 12 months after Crystalens(R) accommodating IOL implantation.

Clinical Results of Crystalens(R) (AT-45) Accommodating Intraocular Lens

PURPOSE: To evaluate one-year clinical results of Crystalens(R) (AT-45, Eyeonics, CA, USA) accommodating IOL implantation. METHODS: In this retrospective study, 25 eyes of 18 patients had phacoemulsification and Crystalens(R) accommodating IOL implantation. Distance and near visual acuity (VA) during the 12-months were measured. RESULTS: At two months, uncorrected distance visual acuity (VA) of 13 eyes (52.0%) and 21 eyes (84.0%) were 20/25 and 20/40 or better, respectively. At six months, 11 eyes (44.0%) and 21 eyes (84.0%) were 20/25 and 20/40 or better, respectively. At 12 months, 11 eyes (44.0%) and 17 eyes (68.0%) were 20/25 and 20/40 or better, respectively. At two months, the uncorrected near VAs of 11 eyes (44.0%) and 17 eyes (68.0%) were 20/25 and 20/40 or better, respectively. At six months, 9 eyes (36.0%) and 16 eyes (64.0%) were 20/25 and 20/40 or better, respectively. After 12 months, 6 eyes (24.0%) and 16 eyes (64.0%) were 20/25 and 20/40 or better, respectively. CONCLUSIONS: The uncorrected near VAs gradually decreased with the passage of time until 12 months after Crystalens(R) accommodating IOL implantation.

Postoperative Refractive Error by Using A-scan in Cataract Surgery After Vitrectomy

PURPOSE: To investigate the difference between target refraction and actual refraction of intraocular lens implantation when cataract surgery was performed after vitrectomy. METHODS: This study evaluated 28 eyes of 28 patients who had undergone vitrectomy without gas tamponade and 25 eyes of 25 patients who had undergone vitrectomy with gas tamponade. A-scans were performed before the respective cataract and vitrectomy surgeries. Three months after cataract surgery, the actual refraction was measured. To compare the difference between the actual and the target refraction calculated by each A-scan, the refractive prediction error was calculated. It is determined by subtracting the target refraction from the actual refraction. RESULTS: In 28 eyes, the mean refractive prediction error calculated by the A-scan performed before vitrectomy was -0.146+/- 0.901D (diopter, D), and the mean refractive prediction error calculated by an A-scan performed just prior to cataract surgery was -0.228+/-1.011D. The two values were not statistically significant (p=0.653). In 25 eyes, the mean refractive prediction errors calculated by A-scans performed before vitrectomy and cataract surgery were -0.171+/-1.079D, and -0.227+/-0.798D, respectively. There was no statistically significant difference between the two values (p=0.563). CONCLUSIONS: When a cataract surgery was performed after vitrectomy, a precise target refraction could be obtained.

The Efficacy of Ranibizumab for Choroidal Neovascularization in Age-related Macular Degeneration

PURPOSE: To report 1-year clinical changes in visual acuity (VA) after intravitreal ranibizumab therapy for choroidal neovascularization (CNV) due to age-related macular degeneration (AMD), and to determine differences in treatment effects according to the CNV subtype. METHODS: Forty six patients (46 eyes) with subfoveal CNV were treated with intravitreal ranibizumab (0.5 mg) injections as needed. Visual acuity, fluorescein angiography, and macular OCT were examined after 12 months. The patients were divided into two groups: Classic CNV and occult CNV. The VA of the two groups was compared 12 months after the initial injections. RESULTS: The average VA and mean central retinal thickness (CRT) before ranibizumab treatment was 1.011+/-0.408 logMAR and 335.3 microm, respectively, and the VA and mean CRT 12 months after the initial injections was 0.928+/-0.357 logMAR and 246.2 microm, respectively (p=0.042, p<0.001). Out of 46 eyes, 13 eyes (28.3%) had a VA that improved by more than 0.1 logMAR, 33 eyes (71.7%) had VA that changed less than 0.1 logMAR, and 40 eyes (86.6%) had a VA that changed by less than 0.3 logMAR. The VA improved to 0.084 logMAR in classic CNV (18 eyes) and to 0.081 logMAR in occult CNV (28 eyes) after 12 months, though the difference between groups was not significant (p=0.910). CONCLUSIONS: Intravitreal injection of ranibizumab is an effective treatment for patients with subfoveal CNV secondary to AMD to improve or stabilize VA, and the effect of treatment on VA is not significantly different according to the CNV subtype.

The Combined Effect of Subtenon Triamcinolone Injection and Panretinal Photocoagulation on Diabetic Retinopathy

PURPOSE: To investigate the result of posterior sub-tenon triamcinolone acetonide injection combined with panretinal photocoagulation (PRP) in patients with diabetic retinopathy. METHODS: A prospective study was performed on patients with diabetic retinopathy who required PRP. The study group consisted of 12 patients (12 eyes) of diabetic retinopathy without clinically significant macular edema (CSME) and 13 patients (13 eyes) with CSME. All patients were injected posteriorly with sub-tenon triamcinolone acetonide (40 mg) one week before PRP. During a six-month follow-up, best-corrected visual acuity, the development of macular edema, changes in fluorescein angiography, and related complications were monitored. RESULTS: During a six-month follow-up, visual acuity was well preserved in patients with diabetic retinopathy without CSME (12 eyes). Only one patient in this group experienced temporary macular edema at 3 months after combined therapy. In the CSME group (13 eyes), the visual acuities of seven patients (53.8%) increased, those of five patients (38.5%) remained same, and one patient's visual acuity (7.7%) decreased in a study period of six months. Fluorescein angiography showed that macular edema was resolved in most patients except in one patient in whom macular edema remained for up to 6 months. Complications from combined therapy occurred in two patients who showed slight and temporary increase of intraocular pressure. CONCLUSIONS: Combined treatment with posterior sub-tenon triamcinolone acetonide injection and PRP may provide benefits for patients with diabetic retinopathy who require urgent PRP by preventing exacerbation of macular edema.

The Relationship Between the Density of Lens and Liquefaction Time Using Liquefaction Device

PURPOSE: To investigate the effect of lens density on liquefaction time by using liquefaction device (AquaLase(R), Alcon Laboratories, TX, U.S.A.). METHODS: Cataract surgery using AquaLase(R) was performed on 47 eyes. With a Scheimpflug camera, the density and thickness of lens were measured in eye of each patient preoperatively. During surgery, liquefaction time and total number of pulses were recorded. The correlation of both density and thickness of lens with liquefaction time and total number of pulses was analyzed. RESULTS: The mean density of anterior cortex, nucleus, and posterior cortex was 112.45+/-42.1 computer compatible tapes (CCT), 76.5+/-22.7 CCT, and 70.9+/-52.2 CCT, respectively. The mean thickness was 0.97+/-0.30 mm, 2.76+/-0.54 mm, and 0.81+/-0.24 mm, respectively. The mean liquefaction time was 174.8+/-108.2 seconds. The mean total number of pulses was 4799+/-3007.There was no significant difference between the density of each area of lens (anterior cortex, nucleus, posterior cortex, and total lens) and liquefaction time (p>0.05), and between the thickness of each area of lens and liquefaction time (p>0.05). There was no significant difference between the density of each area of lens and total number of pulses (p>0.05), and between the thickness of each area of lens and total number of pulses (p>0.05). CONCLUSIONS: When extraction of soft to moderate density cataract was performed with AquaLase(R), liquefaction time and total number of pulse did not correlate to the density and thickness of lens.