N-acetylcysteine protects against chorioretinal damage induced by photodynamic therapy for experimental choroidal neovascularization in a rat model.

PURPOSE: We explored the protective effects of N-acetylcysteine (NAC) on chorioretinal damage induced by photodynamic therapy (PDT) in an experimental rat model of choroidal neovascularization (CNV). METHODS: Experimental CNV was induced by an argon laser in 24 Brown Norway rats 7 days prior to PDT. Commencing 1 day after CNV induction, 0.5 mL of NAC was orally administered daily to the NAC + group (12 rats), and 0.5 mL of normal saline to the NAC- group (12 rats). Diode laser treatment was delivered for 42 s (total energy, 25 J/cm2) to the left eye prior to verteporfin infusion (PDT-) and to the right eye 15-20 min after such infusion (PDT+). Fluorescein angiography was performed just prior to PDT and enucleation to evaluate fluorescein leakage and CNV closure. We compared the CNV thickness, PDT-induced apoptosis [evaluated via terminal dUTP nick-end labeling (TUNEL)], fluorescein angiographic data, and extents of immunohistofluorescent staining for cleaved caspase-3 and superoxide dismutase (SOD) between the two groups. RESULTS: Fourteen days after diode laser treatment, the CNV closure rate was significantly higher in the PDT-treated than the control group. However, the CNV closure rates did not differ significantly between the NAC- and NAC + groups. The TUNEL activity (a measure of PDT-induced apoptosis) of retinal cells was higher in the NAC-/PDT + than the NAC+/PDT + group at 1, 3, 7, and 14 days. The cleaved caspase-3 and SOD levels were higher in the NAC-/PDT + than the NAC+/PDT + group at 3 and 7 days. CONCLUSIONS: PDT triggers oxygen radical-induced injury to, and apoptosis in, the retina. NAC may reduce PDT-induced damage to the retina without compromising the therapeutic efficacy of CNV.

Aqueous levels of erythropoietin in acute retinal vein occlusion with macular edema.

AIM: To investigate the aqueous erythropoietin (EPO) levels and associated factors in patients with acute retinal vein occlusion (RVO). METHODS: The aqueous EPO level was measured in patients with macular edema (ME) secondary to acute branched retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO). Aqueous fluid from cataract patients served as the control. We also evaluated whether aqueous level of EPO was associated with factors such as serum EPO level, non-perfusion area, central macular thickness (CMT), and arterio-venous (AV) transit time. RESULTS: Twenty-seven RVO patients (16 BRVO, 11 CRVO) and 9 control subjects were enrolled in the study. The aqueous EPO level (mU/mL) was higher in RVO (68.2±54.3) than that in the control subjects (12.9±5.9). More specifically, the aqueous EPO level was higher in CRVO (118.9±52.1) than that in BRVO (33.3±10.8). However, no differences were found in serum EPO levels among three groups. CMT in RVO patients had a positive correlation with the aqueous EPO level (r=0.66). Also, in terms of non-perfusion area, the aqueous EPO levels were more elevated in the ischemic subgroup than in the non-ischemic subgroup in both BRVO and CRVO. CONCLUSION: Aqueous EPO levels are elevated in patients with macular edema secondary to recent onset RVO. Patients with CRVO have higher EPO levels than those with BRVO. The aqueous EPO level in RVO has a positive correlation with CMT and is associated with non-perfusion area. These results suggest that the aqueous EPO level could be associated with retinal ischemia and may be involved in the pathogenesis of macular edema secondary to RVO.

Spontaneous resolution of intravitreal steroid-induced bilateral cytomegalovirus retinitis.

A 73-year-old woman underwent vitrectomy and intravitreal triamcinolone acetonide (IVTA) of the right eye and cataract surgery with IVTA of the left eye, for bilateral diabetic macular edema. The patient presented with visual loss in both eyes three-months postoperatively. The fundoscopic examination revealed white-yellow, necrotic peripheral lesions in the superotemporal quadrant of both eyes. Although bilateral acute retinal necrosis was suspected, azotemia resulting from diabetic nephropathy limited the use of acyclovir. Antiviral treatment was not started. A sample of the aqueous humor for polymerase chain reaction (PCR) analysis was obtained. One week later, the PCR results indicated the presence of cytomegalovirus (CMV). Since the retinal lesions did not progress and did not threaten the macula, the patient was followed without treatment for CMV. The retinal lesions progressively regressed and completely resolved in both eyes by six months of follow-up. Patients with IVTA-induced CMV retinitis may not require systemic treatment with ganciclovir.

Chronic kidney disease, early age-related macular degeneration, and peripheral retinal drusen.

PURPOSE: To evaluate the association between chronic kidney disease (CKD) and early age-related macular degeneration (AMD) and peripheral retinal drusen in Korean adults 50 years and older. METHODS: This study included 3008 participants aged 50-87 years. Early AMD was assessed from retinal photographs based on modified Wisconsin AMD grading system and peripheral retinal drusen were assessed with a standardized examination. We defined CKD as estimated glomerular filtration rate of 60mL/min/1.73m(2) and below according to the Modification of Diet in Renal Disease equation. Logistic regression was used to examine the association between early AMD, peripheral retinal drusen, and CKD. RESULTS: There were 88 subjects with early AMD and 42 subjects with peripheral retinal drusen. After adjusting for age, gender, body mass index, smoking status, hypertension, and diabetes mellitus, a significant association was found between CKD and peripheral retinal drusen as well as early AMD. Subjects with CKD were more likely to have early AMD (OR, 1.68; 95% CI, 1.04-2.72) and peripheral retinal drusen (OR, 2.01; 95% CI, 1.02-3.99) than those without CKD. CONCLUSIONS: CKD was associated with peripheral retinal drusen as well as early AMD in Korean adults 50 years and older.

Diabetes mellitus and early age-related macular degeneration.

OBJECTIVE: To examine the association of diabetes mellitus and early age-related macular degeneration (AMD) in Korean adults 50 years and older. METHODS: This study included 3008 participants aged 50 to 87 years. Early AMD was assessed from retinal photographs based on a modified Wisconsin AMD grading system. Diabetes mellitus was defined as a fasting glucose level of 126 mg/dL or greater or the use of antidiabetic medications. Logistic regression was used to examine the association between diabetes mellitus and early AMD. RESULTS: There were 88 subjects with early AMD and 315 subjects with diabetes mellitus. After adjusting for age, sex, current smoking, obesity, and hypertension, significant association was found between diabetes mellitus and early AMD. Subjects with diabetes mellitus were more likely to have early AMD (odds ratio, 1.87; 95% confidence interval, 1.07-3.28) than were those without diabetes mellitus. CONCLUSION: There is a relationship between diabetes mellitus and early AMD in Korean adults 50 years and older. The underlying biological processes remain to be determined.

Intravitreal triamcinolone and bevacizumab as adjunctive treatments to panretinal photocoagulation in diabetic retinopathy.

BACKGROUND/AIMS: To evaluate efficacy of intravitreal triamcinolone (IVTA) and bevacizumab (IVB) as adjunctive treatments to panretinal photocoagulation (PRP). METHODS: In 91 eyes of 76 patients (clinically significant macular oedema (CSME) 46 eyes; no CSME 45 eyes) with severe diabetic retinopathy, PRP with IVTA (IVTA group, 30 eyes) or PRP with IVB (IVB group, 31 eyes) or PRP only (PRP group, 30 eyes) was performed. Primary outcome measures were changes in best corrected visual acuity (BCVA) and central macular thickness (CMT) at 1 and 3 months. Secondary outcome measures were proportion of visual gain or loss, and decreased or increased CMT. RESULTS: There was significant worsening in BCVA from 0.26 to 0.29 at 1 and 3 months (p=0.031) in the PRP group. In eyes with CSME, there was significant improvement of BCVA from 0.33 to 0.27 at 1 and 3 months (p=0.012) in IVTA group. In eyes without CSME, PRP group showed significant worsening in BCVA from 0.18 to 0.26 at 1 month (p=0.008) and 0.27 at 3 months (p=0.005). There was significant improvement in CMT in IVTA and IVB groups: in eyes without CSME, there was significant increase in CMT from 209.75 to 259.00 microm at 1 month (p=0.023) and to 276.14 microm at 3 months (p=0.011) in the PRP group; in eyes with CSME, the proportion of eyes with visual gain and decreased CMT was significantly higher in the IVTA group (75% and 100%, respectively) than in the IVB group (37.5% and 62.5%, respectively). CONCLUSIONS: IVTA and IVB may be effective adjunctive treatments to PRP, minimising the risk of PRP-induced macular oedema and visual loss.

Hereditary and clinical features of retinitis pigmentosa in Koreans.

There has been no report about hereditary and clinical features of retinitis pigmentosa (RP) in Koreans. To evaluate these, data were collected from 365 RP patients including age, gender, visual acuity (VA), spherical equivalent (SE) of refractive errors, funduscopic findings, color vision test, visual field score (VFS) obtained from Goldmann perimetry, and the inheritance patterns from pedigrees. Simplex RP was the most common inheritance pattern (61.9%); followed by autosomal recessive RP (17.3%), autosomal dominant RP (12.1%) and X-linked recessive RP (8.8%). Myopia was the most common refractive errors (77.5%) including 16.1% of high myopia. The most common cataract type was posterior subcapsular cataract (25.8%). Observed retinal findings included changes of retinal pigment epithelium (88.8%), bony spicule-like pigmentation (79.7%), attenuation of retinal vessel (76.2%), waxy disc pallor (12.6%), golden ring around optic disc (2.2%), epiretinal membrane (0.8%) and cystoid macular edema (0.5%). Corrected VA and refractive errors did not show any significant difference between the inheritance patterns. VFS was significantly worse in autosomal recessive RP than in autosomal dominant RP. Color vision defect was noted in 66.1% on Hardy-Rand-Rittlers color vision test. In conclusion, Korean RP patients have the indigenous hereditary and clinical features as well as the ordinary ones.

Chorioretinal ischemia and angiogenic milieu following photodynamic therapy.

PURPOSE: To investigate the development of chorioretinal ischemia and expression of angiogenic factors following photodynamic therapy (PDT) in normal rat chorioretina. MATERIALS AND METHODS: Pimonidazole (hypoxia marker) was intraperitoneally administrated 15 min before PDT (to identify the intra-PDT ischemia) and at 10 days and 20 days after PDT (to identify post-PDT ischemia) in 14 Brown-Norway rats (4 rats at each point and 2 rats serving as controls). After enucleation and cryosection at each point, immunohistofluorescent (IHF) staining for pimonidazole was evaluated with confocal scanning microscopy. In another 14 rats, the expression of angiogenic factors following PDT was demonstrated in PDT-irradiated normal chorioretina. Four rats were randomly selected at 3, 7, and 14 days following PDT with 2 rats serving as controls (verteporfin-/laser-). The expressions of vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), and hypoxia-inducible factor (HIF)-1a were evaluated at each point. Diode laser (689 nm, 25 J/cm(2)) was irradiated before verteporfin infusion in the left eye (verteporfin-/laser+) and after infusion in the right eye (verteporfin+/laser+) in each experiment. RESULTS: Intensity of pimonidazole uptake increased during PDT and at 10 and 20 days following PDT. The intensity of pimonidazole was the most pronounced immediately after PDT irradiation, but VEGF expression was rarely detected immediately after PDT. VEGF, IGF, and HIF-1a expression increased at 3 days and 7 days. At 14 days after PDT, the expression of VEGF was sustained, but that of IGF and HIF-1a was irregular. CONCLUSIONS: These results show that significant chorioretinal ischemia develops in the irradiated area following PDT and that the ischemia is most pronounced during PDT irradiation. Along with post-PDT overexpression of angiogenic factors, this may be a mechanism contributing to PDT resistance or recurrence of chorioretinal neovascular lesions.

Prognostic factors related to photodynamic therapy for central serous chorioretinopathy.

BACKGROUND: To investigate the effects and prognostic factors related to photodynamic therapy (PDT) for central serous chorioretinopathy (CSC). METHODS: Retrospective medical record reviewing of consecutive CSC patients (chronic or persistent typical CSC) treated with conventional PDT (full-dose verteporfin, laser (689 nm) delivery for 83 s, total light energy of 50 J/cm(2)) was performed. Besides overall anatomic and functional outcomes, the prognostic influences of various baseline factors (sex, age, duration of symptoms, presence of focal leak and pigment epithelial detachment (PED), SRF size, confluent RPE atrophy, PDT spot size), disintegrity of the junction between foveal outer and inner photoreceptor layer (OS-IS) after resolution, and post-treatment RPE changes on outcomes were evaluated. RESULTS: Forty patients (41 eyes) were included. Anatomic success, defined as complete resolution of serous fluid on optical coherence tomography performed 4-6 weeks after PDT, was achieved in 87.8% of eyes, and visual acuity improved significantly (0.19 +/- 0.24 lines). Visual acuity had improved more than one line in 46.3% of the patients and decreased more than one line in 14.6% of patients at the 1-month follow-up visit. Prolonged symptom duration (> 9 months), PED, confluent RPE atrophy, foveal OS-IS disintegrity, and post-PDT RPE changes were associated significantly with visual loss of more than three lines and foveal atrophy. Central macular thickness was significantly reduced in patients treated with PDT compared to those treated with focal laser. CONCLUSIONS: PDT for CSC was effective with regard to anatomic and functional outcomes. However, visual improvement may be limited in patients with prolonged symptom duration, baseline confluent RPE atrophy, foveal OS-IS disintegrity, or progression of RPE atrophy after PDT and the risk of PDT-induced foveal injury should be considered.

Panretinal photocoagulation combined with intravitreal bevacizumab in high-risk proliferative diabetic retinopathy.

PURPOSE: To evaluate the efficacy and safety of intravitreal bevacizumab as an adjunctive treatment to panretinal photocoagulation (PRP) for high-risk proliferative diabetic retinopathy with or without clinically significant macular edema (CSME). METHODS: In forty-one eyes with high-risk proliferative diabetic retinopathy, intravitreal bevacizumab (1.25 mg/0.05 mL) before PRP (Plus group) or PRP alone (PRP group) was performed. Primary outcome measures were changes in best-corrected visual acuity and central macular thickness (CMT). Secondary outcome measures were the proportion of visual loss >/=0.1 logMAR, increase in CMT >/=50 mum, and eyes with development of vitreous hemorrhage. RESULT: Best-corrected visual acuity was significantly worse at 3 months (P = 0.041) in the PRP group, whereas in the plus group, there was no significant change. Central macular thickness decreased significantly at 1 month and 3 months (P = 0.012, 0.008) in the Plus group, whereas in the PRP group, there was no significant change. In eyes with CSME, there was no significant change in best-corrected visual acuity in both groups. Central macular thickness decreased significantly at 1 month and 3 months (P = 0.003, 0.001) in the Plus group, whereas in the PRP group, there was no significant change. In eyes without CSME, best-corrected visual acuity was significantly worse at 1 month and 3 months (P = 0.047, 0.011) in the PRP group, whereas in the Plus group, there was no significant change. Central macular thickness was significantly worse at 1 month and 3 months (P = 0.004, 0.016) in the PRP group, whereas in the Plus group, there was no significant change. In eyes without CSME, the proportion of eyes with visual loss >/=0.1 logMAR at 1 month was significantly higher in the PRP group than in the Plus group (P = 0.020). The proportion of eyes with development of vitreous hemorrhage was significantly lower in the Plus group than in the PRP group (P = 0.023). CONCLUSION: Intravitreal bevacizumab before PRP can be an effective adjunctive treatment to PRP in the treatment of high-risk proliferative diabetic retinopathy, especially if there is not CSME.

Short term effects of topical cyclosporine and viscoelastic on the ocular surfaces in patients with dry eye.

PURPOSE: To compare the short term effects of topical 0.05% cyclosporine (CsA) and a mixture of 0.08% chondroitin sulfate and 0.06% sodium hyaluronate (CS-HA) on dry eye ocular surfaces. METHODS: 36 patients with moderate to severe dry eye (5 mm/5 min or less with Schirmer's test or tear break up time (BUT) less than 6 seconds), were treated with topical application of CS-HA on one eye and CsA on the other 4 times a day for 6-8 weeks. BUT, Schirmer's test without anesthesia, and conjunctival impression cytology (CIC; goblet cell density, nucleus to cytoplasmic ratio, and epithelial cell morphology) were evaluated and compared between eyes before and after treatment (repeated measurement of ANOVA). RESULTS: After treatment, BUT and tear wettings were significantly prolonged in each group. Topical CsA treated eyes had greater increase in BUT (p=0.026); there was no significant difference in tear wetting (p=0.132). While the 3 parameters of CIC improved in both groups, goblet cell density was significantly higher in eyes treated with CsA (p=0.033). CONCLUSIONS: While both CS-HA and 0.05% CsA eyedrops improve ocular surfaces, topical CsA may have a better effect on enhancing tear film stability and goblet cell density.

Effect of subconjunctivally injected, liposome-bound, low-molecular-weight heparin on the absorption rate of subconjunctival hemorrhage in rabbits.

PURPOSE: To investigate the effect of subconjunctival injection of liposome-bound, low-molecular-weight heparin (LMWH) on the absorption rate of subconjunctival hemorrhages. METHODS: Subconjunctival hemorrhages were induced in both eyes of 30 rabbits by the subconjunctival injection of 0.1 mL of autologous blood from auricular marginal veins. After 8 hours, randomized subconjunctival injections of one of three materials were made: 5 IU/mL liposome-bound LMWH (0.1 mL) in 18 eyes (group A), only liposomes (0.1 mL) in 14 eyes (group B), the free form of LMWH (5 IU/mL, 0.1 mL) in 14 eyes (group C), or no injection in 14 eyes (group D). Subconjunctival hemorrhages were photographed with a digital camera at 8, 24, 48, 72, 96, and 120 hours after induction of subconjunctival hemorrhages, sized with an image analyzer, and compared between groups. RESULTS: Subconjunctival hemorrhages were absorbed faster in group A (liposome-bound LMWH injected) than in with group B (liposome injected). Comparison of groups A and C (free LMWH injected) showed statistical differences in the absorption rates at 96 and 120 hours except at 24, 48, and 72 hours. The mean elapsed time for the complete resorption of subconjunctival hemorrhages was shortest in group A among four groups, whereas group B and the control showed no significant differences. The ocular and systemic absorption of LMWH were significantly lower after injection of the liposome-bound than the free form. CONCLUSIONS: The subconjunctival injection of liposome-bound LMWH appears to enhance subconjunctival hemorrhage absorption in rabbits.

The effect of contact lens wear on the ocular surface changes in keratoconus.

PURPOSE: To investigate the effects of contact lens wear or the keratoconic shape itself on the changes in the ocular surface in keratoconus. METHODS: Forty-two patients (84 eyes) were enrolled in this study and divided into four groups. Group 1 comprised 22 eyes with keratoconus that had been wearing rigid gas-permeable (RGP) contact lenses for an average of 5.54 +/- 2.11 years. Group 2 comprised 24 myopic eyes that had been wearing RGP contact lenses for 6.42 +/- 1.79 years. Group 3 comprised 20 eyes with keratoconus without any contact lens wear. Group 4 comprised 18 healthy eyes that were used as controls. The ocular surface changes were evaluated by determining the tear film breakup time and performing conjunctival impression cytology. The goblet cell densities, nucleus-to-cytoplasm ratio, and epithelial cell morphology in the four groups were compared with optical microscopy in the high-power field. RESULTS: The tear film breakup times in groups 1 and 2 were significantly lower than those in groups 3 and 4. The goblet cell densities were 5.49 +/- 1.75 and 5.82 +/- 1.63 in groups 1 and 2, respectively, which were significantly lower (P < 0.05) than the 8.79 +/- 1.42 and 10.24 +/- 2.10 in groups 3 and 4, respectively. There were no statistically significant differences in the goblet cell densities, nucleus-to-cytoplasm ratios, and epithelial cell morphologies between groups 1 and 2 and groups 3 and 4. CONCLUSIONS: The ocular surface changes in keratoconus may be directly related to contact lens wear and not to the keratoconic shape itself.

Correction of lower lid retraction combined with entropion using an ear cartilage graft in the anophthalmic socket.

PURPOSE: To investigate the surgical results of an ear cartilage graft and supplemental procedures for correcting lower lid retraction combined with entropion in anophthalmic patients. METHODS: We reviewed retrospectively the medical records of 7 anophthalmic patients with lower lid retraction and entropion, who received a posterior lamellar ear cartilage graft and one or both of lateral tarsal strip or eyelash-everting procedure between March 1998 and March 2003. Preoperative and postoperative lid and socket statuses were also investigated. RESULTS: Ear cartilage grafts were performed in all 7 patients, lateral tarsal strips in 6, and eyelash-everting procedures in 5. Postoperative follow-up durations ranged from 4 to 28 months (average 12.6 months). Retractions were corrected during follow-up in all patients. There were no cases of entropion immediately after surgery. However, the eyelashes of the lower lid returned to an upright position in 4 patients, but not so severe as to touch the ocular prosthesis, and thus did not require surgical correction during follow up. CONCLUSIONS: Lower lid retraction combined with entropion in anophthalmic patients can be corrected effectively using an ear cartilage graft with selective, supplemental procedures.