The effect of nondamaging subthreshold laser therapy in patients with chronic central serous chorioretinopathy.

PURPOSE: To evaluate the efficacy of nondamaging subthreshold laser therapy in Korean patients with chronic central serous chorioretinopathy (cCSC). METHODS: This retrospective interventional case series included 31 patients (31 eyes) with cCSC who underwent nondamaging laser therapy using Endpoint Management (EpM) software. Since a barely visible burn of the test spot was defined as 100% pulse energy, 30% pulse energy with a 200-µm spot was titrated to treat the macular area based on EpM settings. A 30% pulse laser with a spacing of 0.25-beam diameter was applied to cover the macular area where hyperfluorescent leaks were observed on fluorescein angiography. Changes in central macular thickness (CMT), subretinal fluid (SRF) height, subfoveal choroidal thickness (SCT), and logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) were measured at baseline and after 3 and 6 months. If the subretinal fluid persisted for 3 months, retreatment was performed. RESULTS: At 6 months post-treatment, the complete SRF resolution rate was 48.39% (15/31 eyes), and the partial SRF resolution rate was 12.90% (4/31 eyes). The change in mean BCVA (logMAR) was not significant (0.31 ± 0.29 at the baseline and 0.31 ± 0.40 at month 6) (p = 0.943). At the baseline, the mean CMT (µm) decreased from 350.74 ± 112.76 at baseline to 239.71 ± 130.25 at month 6 (p < 0.001), and the mean SRF height (µm) decreased from 193.16 ± 90.69 at baseline to 70.58 ± 100.00 at month 6 (p < 0.001). However, the change in SCT was not statistically significant (p = 0.516). In 15 patients who were retreated at month 3, the mean SRF height (µm) decreased significantly from 144.67 ± 74.01 at month 3 to 77.13 ± 63.77 at month 6 (p = 0.002). No side effects associated with laser therapy were observed during the 6-month follow-up. CONCLUSIONS: Nondamaging laser therapy with a modified macular treatment was effective in reducing CMT and SRF and showed favorable visual and anatomical outcomes in patients with cCSC.

Comparison of intravitreal preservative-free triamcinolone versus posterior sub-tenon triamcinolone acetonide injection for bevacizumab-resistant diabetic macular edema.

BACKGROUND: Triamcinolone acetonide (TA) is administered as an intravitreal or posterior sub-Tenon's capsule injection, as treatment for diabetic macular edema (DME). The intravitreal use of TA is limited because commercially available triamcinolone acetonide contains benzyl alcohol, a neurotoxic preservative. Few studies have compared effects of preservative-free intravitreal TA (IVTA) and posterior sub-Tenon capsule TA (STTA) injections for DME. Thus, herein, we compared the effectiveness of preservative-free IVTA and STTA for treatment of bevacizumab-resistant DME. METHODS: In this retrospective cohort study, bevacizumab-resistant DME was defined as a lack of response to at least three consecutive intravitreal bevacizumab (IVB) injections. Changes in mean central macula thickness (CMT), best-corrected visual acuity (BCVA), and intraocular pressure (IOP) between IVTA and STTA groups were compared at baseline and at 1, 2, and 3 months after treatment. RESULTS: Forty eyes from 40 patients were included in this study. In the IVTA group, the mean CMT improved significantly from 400.2 ± 144.42 µm at baseline to 288.35 ± 151.74 µm at 3 months after treatment (p = 0.01). Similarly, in the STTA group, the mean CMT improved significantly from 446.65 ± 120.74 µm at baseline to 382.9 ± 113.58 µm at 3 months after treatment (p = 0.009). The mean BCVA of the IVTA group also showed improvement, decreasing from 0.75 ± 0.55 logarithm of the minimum angle of resolution (logMAR) at baseline to 0.625 ± 0.50 logMAR at 3 months after treatment (p = 0.089). Similarly, the mean BCVA of the STTA group improved, from 0.6 ± 0.36 logMAR at baseline to 0.54 ± 0.35 logMAR at 3 months after treatment (p = 0.094). CONCLUSION: Given that IVTA and STTA demonstrated statistically equivalent anatomical and functional effects in patients with bevacizumab-resistant DME, the less invasive STTA may be considered the preferred treatment approach for the management of bevacizumab-resistant DME. TRIAL REGISTRATION: Retrospectively registered.

The Effect of Selective Retina Therapy for Bevacizumab-Resistant Chronic Central Serous Chorioretinopathy.

PURPOSE: The aim of this study was to evaluate the efficacy of selective retina therapy (SRT), used in conjunction with real-time feedback dosimetry (RFD), in the treatment of bevacizumab-resistant chronic central serous chorioretinopathy (CSC). PATIENTS AND METHODS: In this retrospective cohort study, 22 eyes of 22 patients with bevacizumab-resistant chronic CSC, showing focal or diffuse foveal leakages on fundus fluorescein angiography (FFA), were included. After evaluation of the test spots at temporal arcades, SRT (wavelength, 527 nm; pulse repetition rate, 100 Hz; ramping over maximal 15 micropulses; and spot diameter, 200 µm) using RFD was applied to the leakage sites observed on FFA. Changes in the mean best-corrected visual acuity (BCVA), central macular thickness (CMT), and subretinal fluid (SRF) height were evaluated at baseline and at 1, 3, 6, 9, and 12 months following treatment. RESULTS: SRF completely resolved in 81.8% (18/22 eyes) cases at 12 months post-treatment. The mean BCVA (logarithm of the minimum angle of resolution [logMAR]) improved from 0.49 ± 0.29 at baseline to 0.43 ± 0.36 at 12 months (p = 0.067). The mean BCVA gain was 0.06 logMAR, equivalent to 3 ETDRS letters. The CMT significantly decreased from 323 ± 85.6 µm at baseline to 221.5 ± 60.4 µm at 12 months (p < 0.001). The mean SRF height also significantly decreased from 174.6 ± 86.4 µm at baseline to 35.1 ± 75.4 µm at 12 months (p < 0.001). CONCLUSION: SRT showed favorable visual and anatomical outcomes in patients with bevacizumab-resistant chronic CSC.

Retinal pigment epithelial responses based on the irradiation density of selective retina therapy.

PURPOSE: We evaluated the response of the retinal pigment epithelium (RPE) to high-density (HD) or low-density (LD)-selective retina therapy (SRT) with real-time feedback-controlled dosimetry (RFD) in rabbits. METHODS: Sixteen eyes of 8 Chinchilla Bastard rabbits underwent SRT with RFD (527-nm wavelength, 1.7-µs pulse duration), using automatically titrated pulse energy, by using optoacoustic dosimetry or real-time reflectometry. Fifty-six 25-µJ SRT, including LD-SRT (1-spot or 2-spot-spacing) and HD-SRT (4-spot, 7-spot, or 9-spot-no-spacing), were applied per eye. Color fundus photography and fundus fluorescein angiography (FFA) were used to confirm SRT spots 1-h post-SRT. Light microscopy and scanning electron microscopy (SEM) were performed at 2-h, 3-day, 7-day, and 1-month post-treatment. RESULTS: We tested 896 spots irradiated by SRT with RFD and confirmed that SRT lesions were adequate, based on invisibility on fundoscopy and visibility on FFA. On SEM, at 2-h post-SRT, flattened RPE cells were observed in the center of the SRT lesion. While normal RPE cells were clearly observed between LD-SRT lesions, healthy RPE cells were rare in HD-SRT lesions at 2-h post-treatment. At 7-day post-SRT, SEM revealed completely restored LD-SRT lesions with small or large RPE cells with microvilli, whereas HD-SRT lesions were covered with RPE cells without microvilli. At 1-month post-SRT, SEM revealed restored RPE cells with microvilli in HD-SRT lesions. On light microscopy, both HD- and LD-SRT lesions were completely restored with adjacent RPE cells and spared photoreceptors at 1-month post-treatment. CONCLUSIONS: Although both HD- and LD-SRT lesions had recovered at 1-month post-SRT, LD-SRT lesions healed faster than HD-SRT lesions.

One-Year Functional and Anatomical Outcomes After Selective Retina Therapy With Real-Time Feedback-Controlled Dosimetry in Patients With Intermediate Age-Related Macular Degeneration: A Pilot Study.

BACKGROUND AND OBJECTIVES: This pilot study sought to evaluate changes in macular function and drusen volume (DV) after selective retina therapy (SRT) in patients with intermediate age-related macular degeneration (iAMD). STUDY DESIGN/MATERIALS AND METHODS: Twenty participants with bilateral iAMD were included in this prospective interventional case series study. After titrating pulse energy by real-time feedback-controlled dosimetry, SRT with a wavelength of 527 nm was applied around the macula of one eye of each patient. Changes in best-corrected visual acuity (BCVA), DV within the central 5-mm ring (C5), and retinal sensitivity (RS) of the SRT-treated eyes (treated eyes) and untreated fellow eyes (untreated eyes) were evaluated at baseline and then at 3, 6, 9, and 12 months after treatment using linear mixed models. RESULTS: The mean BCVA did not change significantly between baseline and 12 months in both treated and untreated eyes (P = 0.06, P = 0.24, respectively), whereas the BCVA increase rate was faster for treated than for untreated eyes at the 12-month visit (-0.072 logMAR; 95% confidence interval [CI], -0.085 to -0.059 logMAR; P = 0.006). The mean cube root transformation of DV (cube root DV) within C5 in the untreated eyes increased significantly from 0.278 ± 0.115 at baseline to 0.295 ± 0.132 mm (P = 0.027) at 12 months, whereas the cube root DV change in treated eyes was not significant (P = 0.553). The rate of increase in the cube root DV was lower in treated than in untreated eyes at the 12-month visit (-0.016 mm; 95% CI, -0.018 to -0.011 mm; P = 0.015). The mean RS was increased from 22.49 ± 2.40 dB to 24.09 ± 2.19 dB (P < 0.001) in the treated eyes, whereas the change of mean RS in the untreated eyes was not significant at the 12-month visit (P = 0.18). The treated eyes had a higher rate of increase in RS than untreated eyes at the 12-month visit (1.012 dB; 95% CI, 0.776-1.251 dB; P = 0.037). The RS change was significantly associated with the interaction between SRT treatment and time (P = 0.028), whereas it was not associated with cube root DV change (P = 0.106). No SRT-related adverse effects were observed in all participants during the 1-year follow-up. CONCLUSION: Since SRT improved the mean RS and reduced the rate of change in drusen load in the treated eyes, as compared to the untreated eyes, SRT might slow the progression of iAMD. However, further large randomized clinical trials are necessary to confirm the efficacy of SRT for iAMD. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

The efficacy of selective retina therapy for diabetic macular edema based on pretreatment central foveal thickness.

To evaluate the efficacy of selective retina therapy (SRT) in patients with diabetic macular edema (DME) based on pretreatment central foveal thickness (CFT). Seventy-two eyes of 63 patients with DME who had previously undergone SRT were included. Patients were divided into two groups based on the CFT at baseline. Group 1 was composed of 35 eyes with CFT < 400 µm and group 2 was composed of 37 eyes with CFT ≥ 400 µm. Changes in best corrected visual acuity (BCVA) and CFT were measured at baseline, 3 and 6 months after SRT. A single-session retreatment was performed at 3-month posttreatment if there was no reduction in CFT. Rescue treatment with intravitreal anti-VEGF injections was performed if persistent DME or vision loss of 1 ≥ logMAR VA line was observed by 6 months after initial SRT. Six months after SRT, group 1 showed reduction of 45.9 µm in mean CFT (P < 0.001) and gain of 0.13 logMAR in mean BCVA (P < 0.001), whereas group 2 experienced no significant change in CFT or BCVA. In group 1, retreatments were performed in 6 eyes (17.1%), and rescue treatment was performed in 1 eye (2.9%), whereas in group 2, retreatment was performed in 17 eyes (45.9%), and rescue treatments were administered in 27 eyes (73%) during a 6-month follow-up. Although SRT had limited effects as a treatment for severe DME, SRT monotherapy for mild DME was effective in improving BCVA and reducing CFT during a 6-month follow-up period.

Comparison of pre-retinal oxygen pressure changes after selective retina therapy versus conventional photocoagulation in the rabbit eye.

PURPOSE: To evaluate oxygen consumption by photoreceptors, we estimated changes in pre-retinal oxygen pressure (PO2) after selective retina therapy (SRT) compared with conventional photocoagulation (PC) in rabbits. METHODS: One eye of each of 10 Chinchilla Bastard rabbits received both 144 laser SRT spots and 144 laser PC spots. Color fundus photography, optical coherence tomography (OCT), and fluorescein angiography were used to evaluate the lesions after treatment. Fiber-optic sensors (optodes) were used to determine the pre-retinal PO2 levels of untreated, SRT-treated, and PC-treated areas of laser-damaged eyes 7 days after treatment. The pre-retinal PO2 was measured in the other five eyes (controls). The same procedures were applied to these remaining five eyes 4 weeks after treatment. Light microscopy (LM) was used to evaluate histological changes 7 days and 4 weeks after treatment. RESULTS: We found no significant difference in the mean pre-retinal PO2 values among untreated, SRT-treated, and control eyes 7 days after treatment. However, the mean pre-retinal PO2 value in PC-treated regions (24.3 ± 4.9 mmHg; mean ± SD) was higher than those in untreated regions (17.0 ± 1.8 mmHg; P = 0.019), SRT-treated regions (16.7 ± 2.6 mmHg; P = 0.015), and controls (16.9 ± 2.4 mmHg; P = 0.018). Similarly, the mean pre-retinal PO2 of only PC-treated regions (25.2 ± 4.7 mmHg) was higher than those of the untreated regions (16.3 ± 2.5 mmHg; P = 0.006), SRT-treated regions (17.7 ± 3.1 mmHg; P = 0.023), and controls (16.4 ± 2.4 mmHg; P = 0.007) 4 weeks after treatment. OCT and LM revealed selective retinal pigment epithelium damage with the sparing of photoreceptors in SRT lesions. CONCLUSIONS: SRT treatment did not induce changes in the oxygen consumption of photoreceptors, or the pre-retinal PO2.

Comparison of the tissue response of selective retina therapy with or without real-time feedback-controlled dosimetry.

PURPOSE: The purpose of this study is to evaluate the retinal tissue response upon selective retina therapy (SRT) with or without real-time feedback-controlled dosimetry (RFD) in rabbits. METHODS: Eighteen eyes of nine Chinchilla Bastard rabbits were treated by SRT with or without RFD (Q-switched Nd:YLF, wavelength 527 nm, pulse duration 1.7 µs). RFD operated by optoacoustic and reflectometric methods detects the microbubbles from retinal pigment epithelium (RPE) damage in real time. After SRT, light microscopy (LM) and scanning electron microscopy (SEM) were performed at 1 h, 1 day, 3 days, 7 days, and 1 month. The RPE-damaged area on SEM was measured by ImageJ 1 h after SRT. RESULTS: Without RFD, the RPE-damaged area of 76 SRT-treated spots showed a strong positive correlation with ramping pulse energy (Pearson's correlation coefficient, 0.706; P < 0.001). With RFD, there was a weak positive correlation between the RPE-damaged area of 92 spots and ramping pulse energy (Pearson's correlation coefficient, 0.211; P = 0.044). The detection rate of RFD was 91.8% by evaluating 563 SRT spots. Histology revealed that SRT with RFD produced a selectively disrupted RPE monolayer while sparing the photoreceptor layer inner segment. CONCLUSIONS: RFD can be useful to titrate the pulse energy of visually undetectable SRT treatment.

Selective retina therapy with automatic real-time feedback-controlled dosimetry for chronic central serous chorioretinopathy in Korean patients.

PURPOSE: To evaluate the safety and efficacy of selective retina therapy (SRT) with real-time feedback-controlled dosimetry (RFD) in the treatment of chronic central serous chorioretinopathy (CSC). METHODS: In this retrospective case series study, 50 eyes of 49 patients with chronic CSC demonstrating focal or diffuse foveal leakages on fundus fluorescein angiography (FFA) were included. Following evaluation of test spots at temporal arcades, SRT (wavelength 527 nm, pulse repetition rate 100 Hz, pulse energy ramp with maximal 15 pulses) with retinal spot diameter of 200 µm was applied to the areas of each leakage observed on fluorescein angiography. Changes in mean best corrected visual acuity (BCVA), maximum macular thickness (MMT), subretinal fluid (SRF) height, and subfoveal choroidal thickness (SCT) were evaluated at 1, 2 and 3 months after treatment. RFD was used for adjusting the pulse energy. Eyes received a mean of 21.1 ± 18.1 treatment spots with a range of energies between 50uJ and 200uJ per pulse. RESULTS: Subretinal fluid (SRF) was completely resolved in 74% (37/50 eyes) at month 3. Mean BCVA (LogMAR) was improved from 0.44 ± 0.29 at baseline to 0.37 ± 0.32 at month 3 (p = 0.001). MMT was decreased from 335.0 ± 99.8 µm at baseline to 236.4 ± 66.4 µm after 3 months (p < 0.001). SRF height was decreased from 168.0 ± 77.3 µm at baseline to 29.0 ± 57.3 µm after 3 months (p < 0.001). However, the changes in SCT were not statistically significant (p = 0.48). CONCLUSIONS: SRT treatment with RFD showed favorable visual and anatomical outcomes in patients with chronic CSC.

Safety and efficacy of selective retina therapy (SRT) for the treatment of diabetic macular edema in Korean patients.

PURPOSE: Selective retina therapy (SRT) stimulates retinal pigment epithelium (RPE) cell migration and proliferation into irradiated areas. The objective of this study was to evaluate the efficacy and safety of SRT in Korean patients with clinically significant diabetic macular edema (DME). METHODS: Prospective non-randomized interventional case series study. Twenty-three eyes of 21 patients with clinically significant DME were treated with SRT and followed for 6 months. Patients underwent an evaluation of best corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study (ETDRS) letters. Microperimetry was employed to measure macular sensitivity within the central 10° field, and the central macular thickness (CMT) and maximum macular thickness (MMT) were measured. RESULTS: An improvement in BCVA of one to two ETDRS lines was observed in 41.2 % of patients and an improvement of greater than two lines in 29.4 %. Although there was no significant change in CMT (P > 0.05), MMT decreased from 465.8 ± 87.4 µm to 434.3 ± 83.9 µm (P = 0.006), and mean macular sensitivity increased from 20.8 ± 3.4dB to 22.5 ± 3.5dB (P = 0.02). CONCLUSIONS: The gains in BCVA and improvement in macular sensitivity demonstrated that SRT may be used as an effective and safe treatment modality in Korean patients with clinically significant DME.

Anti-angiogenic effect of ALS-L1023, an extract of Melissa officinalis L., on experimental choroidal neovascularization in mice.

BACKGROUND: The effect of ALS-L1023, an extract of Melissa officinalis L. (Labiatae; lemon balm) leaves, on experimental choroidal neovascularization (CNV) in mice was evaluated. METHODS: C57BL/6 mice were given either vehicle or ALS-L1023 daily via oral gavage for 3 weeks (days 0-21). CNV was induced by rupturing Bruch's membrane using laser photocoagulation (day 7). Two weeks after laser injury (day 21), the CNV lesions were evaluated by an examination of choroidal flat mounts using fluorescein-labelled dextran, immunofluorescence staining with isolectin B4 and fluorescence angiography. The effects of ALS-L1023 on endothelial cell tube formation and the expression of phosphorylated extracellular signal-regulated kinase 1/2 were evaluated using human umbilical vein endothelial cells. RESULTS: The extent of CNV was reduced by ALS-L1023. Mice treated with 100 and 200 mg/kg/day of the material exhibited 44.3 and 68.1% reductions in the extent of CNV lesions, respectively, compared to the vehicle group (P < 0.001). The size of the isolectin B4-labelled area was also significantly decreased in the ALS-L1023-treated groups (P < 0.001). On fluorescein angiography, ALS-L1023-treated mice exhibited significantly less leakage of fluorescent material than did vehicle-treated mice. ALS-L1023 decreased vascular endothelial growth factor-induced human umbilical vein endothelial cell tube formation in a dose-dependent manner. The expression of phosphorylated extracellular signal-regulated kinase 1/2 was suppressed by ALS-L1023. CONCLUSIONS: The laser-induced CNV in mice can be inhibited by ALS-L1023. Therefore, it may have therapeutic potential for the treatment of diseases involving CNV.

One year results of intravitreal ranibizumab monotherapy for retinal angiomatous proliferation: a comparative analysis based on disease stages.

BACKGROUND: Retinal angiomatous proliferation (RAP) has been known as a variant of exudative age-related macular degeneration (AMD) with a unfavorable prognosis. To evaluate the effect of ranibizumab administered initially as three loading doses for patients with various stages of RAP. METHODS: A retrospective chart review of 40 patients (41 eyes) with RAP was conducted. The study divided patients into three groups of Group I (8 eyes in stage I), Group II (17eyes in stage II), and Group III (16 eyes in stage III). All patients received three initial monthly intravitreal injections (0.5 mg) of ranibizumab and were monitored monthly for 12 months. Reinjection of ranibizumab after three initial monthly doses was administered on as-needed basis. The main outcome measures were the change in the mean of best-corrected Snellen visual acuity (BCVA) and central macular thickness (CMT), and the total number of injections received during the 12 months. RESULTS: The mean change in BCVA at 12 months was-0.286,-0.165, and-0.151 (logMAR) in Group I, II, and III, respectively. CMT was also reduced by a mean of 32.72 ± 56.75, 57.45 ± 56.48 and 148.37 ± 98.59 µm. The mean number of injections in Group I was significant lower than those in Group II and III (P < 0.001, P < 0.001, and P = 0.15 for Group I versus Group II, Group I versus Group III, and Group II versus Group III, respectively). CONCLUSIONS: The 12-month follow-up outcomes suggest that three consecutive loading doses of intravitreal ranibizumab is an effective treatment on early stage (stage I) of RAP. Patients in stage I showed a significantly lower recurrence rate than patients in later stages.

Use of a Fundus Image-Based Titration Strategy for Selective Retina Therapy for Central Serous Chorioretinopathy.

Background/Objectives: This study evaluated the clinical outcomes of selective retina therapy (SRT) for treating central serous chorioretinopathy. A fundus image-based titration method was used for laser irradiation. Methods: This retrospective cohort study included 29 eyes (29 patients) that underwent SRT for CSC. Both the pulse energy and number of micropulses were adjusted according to the fundus image. Mean best-corrected visual acuity (BCVA), central foveal thickness (CFT), and subretinal fluid (SRF) height were measured 1, 2, 3, 4, and 6 months after SRT. Mean deviation (MD) was measured using microperimetry at 3 and 6 months post-treatment. Results: At 6 months after SRT treatment, SRF was completely resolved in 89.7% of cases (26/29 eyes). The mean Snellen BCVA significantly improved from 0.34 ± 0.31 logMAR (logarithm of the minimum angle of resolution) (20/40) at baseline to 0.24 ± 0.24 logMAR (20/32) at 6 months (p = 0.009). The 0.1 improvement in mean BCVA is equivalent to a 5-letter gain on the ETDRS chart. The mean CFT decreased significantly from 309.31 ± 81.6 µm at baseline to 211.07 ± 50.21 µm at 6 months (p < 0.001). The mean SRF height also decreased significantly from 138.36 ± 56.78 µm at baseline to 23.75 ± 61.19 µm at 6 months (p < 0.001). The mean MD was improved from -1.56 ± 1.47 dB at baseline to -1.03 ± 2.43 dB at 6 months (p = 0.07) after treatment. Conclusions: SRT using fundus image-based titration can yield favorable functional and anatomical outcomes in the treatment of CSC.

Antiangiogenic effects of tivozanib, an oral VEGF receptor tyrosine kinase inhibitor, on experimental choroidal neovascularization in mice.

We investigated the effects of tivozanib, an oral vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor, on experimental choroidal neovascularization (CNV) in mice. C57BL/6 mice were treated with tivozanib (1 mg/kg/day) or vehicle at the onset (day 0) of the study and experimental CNV was induced by laser photocoagulation the following day. In the other groups, tivozanib or vehicle was started 7 days after the laser photocoagulation to determine the effects of the drug on established CNV. To evaluate changes in the CNV lesions, choroidal flat mounts, fluorescein angiography, immunofluorescence staining with isolectin B4, and histological examinations were performed 14 days after CNV induction. Expression of phosphorylated ERK1/2 in choroidal tissues was measured by western blot analysis to demonstrate the inhibitory effect of tivozanib on intracellular signaling pathways involved in CNV development. Compared to vehicle-treatment, tivozanib suppressed the development of CNV lesions and led to a significant regression of established CNV, reducing the affected areas by 80.7% and 67.7%, respectively. On fluorescein angiography, tivozanib-treated mice had significantly less fluorescence leakage than vehicle-treated mice (P < 0.001). On immunofluorescence staining, the isolectin B4-labeled area was smaller in tivozanib-treated mice (P < 0.001). Phosphorylated ERK 1/2 levels increased after CNV induction by laser application and were suppressed by tivozanib treatment. Tivozanib effectively inhibited the progression of CNV in an experimental CNV model. These results suggest that tivozanib may be a therapeutic alternative for the treatment of neovascular age-related macular degeneration.

Effect of cediranib, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, in a mouse model of choroidal neovascularization.

BACKGROUND: This study was conducted to evaluate the effect of cediranib, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, in a mouse model of laser-induced choroidal neovascularization. METHODS: Choroidal neovascularization was induced in C57BL/6 mice by rupturing Bruch's membrane using laser photocoagulation. Following laser injury, the mice were divided into three groups and administered either vehicle, 1 mg/kg or 5 mg/kg of cediranib daily by oral gavage for 2 weeks. Two weeks after laser injury, the area of choroidal neovascularization lesions was measured by choroidal flat mounts using fluorescein-labelled dextran. Immunofluorescence staining with isolectin IB4 was also used to quantify the choroidal neovascularization lesions. RESULTS: Choroidal flat mount analysis revealed that orally administered cediranib reduced the extent of choroidal neovascularization. The groups treated with 1 and 5 mg/kg/day showed 57.2 and 66.0% reduction of choroidal neovascularization lesions, respectively, compared with the control group treated with vehicle alone (P = 0.012). The size of the fluorescently labelled choroidal neovascularization complex in cediranib-treated groups was much smaller than that from vehicle-treated group (P = 0.035). CONCLUSIONS: Cediranib inhibited laser-induced choroidal neovascularization in mice and may have therapeutic potential for patients with neovascular age-related macular degeneration.

The Risk of Retinal Vein Occlusion in Young Patients with Mental Disorders: A Nationwide Cohort Study.

We investigated the association between mental disorders and the incidence rate of retinal vein occlusion (RVO) in young Korean adults. This nationwide cohort study included subjects aged 20-40 years who underwent the Korean National Health Examination between 2009 and 2012. The diagnoses of RVO and mental disorders were based on the International Classification of Diseases Tenth Revision codes. Multivariate Cox proportional hazard regression models were used to evaluate the objective. In total, 6,891,399 subjects were included at baseline and 6,597,803 subjects (mean age, 30.86 ± 4.99) were finally analyzed for a mean follow-up duration of 7.36 ± 1.13 years, with the mental disorders group followed for 7.27 ± 1.15 years and the non-diagnosed group for 7.37 ± 1.12 years. Among a total of 10,145 subjects diagnosed with RVO, 1304 had been diagnosed with mental disorders, while 8841 had not. Cumulative incidence of RVO demonstrated a substantially higher incidence probability in subjects with mental disorders (log-rank p < 0.0001). Mental disorders were associated with an increased incidence rate of RVO (hazard ratio [HR]: 1.268; 95% confidence interval; [CI]: 1.196-1.344). In the subgroup analysis, subjects with depression, sleep disorder, and anxiety disorder exhibited an increased risk of incidence of RVO in all regression models (all p < 0.001). In conclusion, mental disorders and the incidence rate of RVO were significantly positively correlated in a Korean nationwide population-based cohort study. These findings suggest that mental disorders may also be associated with the pathophysiology of RVO in young adults.

Effects of AFP-172 on COX-2-induced angiogenic activities on human umbilical vein endothelial cells.

PURPOSE: To investigate the angiogenic effect of the free acid of tafluprost (AFP-172) on human umbilical vascular endothelial cells (HUVECs). METHODS: HUVECs cultured in the presence or absence of FP receptor antagonist (10 nM AL-8810) were exposed to escalating concentrations of 10(-7), 10(-6), 10(-5), 10(-4) and 10(-3) M AFP-172 (the free acid of tafluprost). For cell proliferation assays, the numbers of cells were derived from a CellTiter96® Aqueous One Solution Cell Proliferation Assay (Promega) by Microplate reader (Bio-Rad, Benchmark). Endothelial cell migration was evaluated by a BD Biocoat™ Angiogenesis System using FluoroBlok ™ 24-well inserts (BD Biosciences, Bedford, MA). BioTek FLx800 fluorescence plate reader was used for quantitative measurement of fluorescently-labeled invasive vascular endothelial cells. Endothelial capillary-like tube formation was evaluated by BD Biocoat Angiogenesis System using Matrigel Matrix 96-well plate. Real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was used to assess the gene expression of vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2) and endothelial nitric oxide synthase (eNOS). COX-2 protein was detected by immunofluorescent staining and Western blot assay. Student's t-test was used for statistical analysis. RESULTS: 10(-4) M AFP-172 treated cells stimulated the proliferation, migration and tube formation of HUVECs as compared to 10(-5), 10(-6,) 10(-7) M AFP-172 treated cells and control (P < 0.01). RT-PCR showed that incubation of HUVECs with 10(-4) M AFP-172 stimulated the expression of COX-2 mRNA (P < 0.05). Western blot assay revealed that AFP-172 caused cells to increase in COX-2 protein at the concentrations of 10(-4) M. CONCLUSIONS: >AFP-172 showed the angiogenic effects on HUVECs at the concentrations of 10(-4) M by inducing COX-2 protein.

Factors Predicting Response to Selective Retina Therapy in Patients with Chronic Central Serous Chorioretinopathy.

This retrospective study aimed to assess the safety and efficacy of selective retina therapy (SRT) with real-time feedback-controlled dosimetry (RFD) for chronic central serous chorioretinopathy (CSC) and to evaluate factors predictive of treatment response. We included 137 eyes of 135 patients with chronic CSC. SRT was performed to cover each of the leakage areas on fundus fluorescein angiography. Changes in mean best-corrected visual acuity (BCVA), central macular thickness (CMT), and subretinal fluid (SRF) height were evaluated at baseline and at 3 and 6 months after treatment. Complete SRF resolution was observed in 52.6% (72/137 eyes) and 90.5% (124/137 eyes) at 3 and 6 months, respectively. Mean BCVA (logMAR) significantly improved from 0.41 ± 0.31 at baseline to 0.33 ± 0.31 at month 6 (p < 0.001). Mean CMT significantly decreased from 347.67 ± 97.38 µm at baseline to 173.42 ± 30.95 µm at month 6 (p < 0.001). Mean SRF height significantly decreased from 187.85 ± 97.56 µm at baseline to 8.60 ± 31.29 µm after 6 months (p < 0.001). Baseline SRF height was a significant predictive factor for retreatment requirement (p = 0.008). In conclusion, SRT showed favorable anatomical outcomes in patients with chronic CSC. A higher baseline SRF height was a risk factor for retreatment.

Real-world treatment intensities and pathways of macular edema following retinal vein occlusion in Korea from Common Data Model in ophthalmology.

Despite many studies, optimal treatment sequences or intervals are still questionable in retinal vein occlusion (RVO) macular edema. The aim of this study was to examine the real-world treatment patterns of RVO macular edema. A retrospective analysis of the Observational Medical Outcomes Partnership Common Data Model, a distributed research network, of four large tertiary referral centers (n = 9,202,032) identified 3286 eligible. We visualized treatment pathways (prescription volume and treatment sequence) with sunburst and Sankey diagrams. We calculated the average number of intravitreal injections per patient in the first and second years to evaluate the treatment intensities. Bevacizumab was the most popular first-line drug (80.9%), followed by triamcinolone (15.1%) and dexamethasone (2.28%). Triamcinolone was the most popular drug (8.88%), followed by dexamethasone (6.08%) in patients who began treatment with anti-vascular endothelial growth factor (VEGF) agents. The average number of all intravitreal injections per person decreased in the second year compared with the first year. The average number of injections per person in the first year increased throughout the study. Bevacizumab was the most popular first-line drug and steroids were considered the most common as second-line drugs in patients first treated with anti-VEGF agents. Intensive treatment patterns may cause an increase in intravitreal injections.

One-year results of intravitreal ranibizumab with or without photodynamic therapy for polypoidal choroidal vasculopathy.

PURPOSE: To evaluate the safety and efficacy of intravitreal ranibizumab with or without photodynamic therapy (PDT) in the treatment of polypoidal choroidal vasculopathy (PCV) in Korean patients. METHODS: A retrospective chart review of 22 patients (24 eyes) with PCV was conducted. Nine eyes were treated with intravitreal ranibizumab combined with a single session of PDT (group 1), and 15 eyes were treated only with ranibizumab (group 2). Such clinical evaluations as best-corrected Snellen visual acuity, central retinal thickness (CRT) by optical coherence tomography (OCT), fluorescein angiography (FA) and indocyanine green angiography (ICGA) were done at baseline, 1, 3, 6, 9 and 12 months after the first injections. Ranibizumab was reinjected on an as-needed basis guided by OCT, FA and ICGA, or at the doctor's discretion. RESULTS: The mean follow-up duration was 22.5 months (range 12-37). The mean best-corrected visual acuity (logMAR) improved, and the mean CRT decreased throughout 12 months in both groups; no statistically significant difference between the groups was found (p = 0.327, p = 0.073, respectively). The number of ranibizumab injections was not significantly different either (p = 0.555). CONCLUSIONS: Intravitreal ranibizumab with or without PDT for PCV in Korean patients resulted in visual and anatomical improvement over the 1-year follow-up period.