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 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.

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.

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.

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.

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.

Real-world incidence of endopthalmitis after intravitreal anti-VEGF injections in Korea: findings from the Common Data Model in ophthalmology.

OBJECTIVES: The aim of this study was to evaluate the real-world incidence of endophthalmitis after intravitreal anti-vascular endothelial growth factor (VEGF) injections using data from the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). METHODS: Patients with endophthalmitis that developed within 6 weeks after intravitreal anti-VEGF injections were identified in 3 large OMOP CDM databases. RESULTS: We identified 23,490 patients who received 128,123 intravitreal anti-VEGF injections. The incidence rates of endophthalmitis were 15.75 per 10,000 patients and 2.97 per 10,000 injections. The incidence rates of endophthalmitis for bevacizumab, ranibizumab, and aflibercept (per 10,000 injections) were 3.64, 1.39, and 0.76, respectively. The annual incidence has remained below 5.00 per 10,000 injections since 2011 despite the increasing number of intravitreal anti-VEGF injections. Bevacizumab presented a higher incidence rate for endophthalmitis than ranibizumab and aflibercept (incidence rate ratio, 3.17; p=0.021). CONCLUSIONS: The incidence of endophthalmitis after intravitreal anti-VEGF injections has stabilized since 2011 despite the explosive increase in anti-VEGF injections. The off-label use of bevacizumab accounted for its disproportionately high incidence of endophthalmitis. The OMOP CDM, which includes off-label uses, laboratory data, and a scalable standardized database, could provide a novel strategy to reveal real-world evidence, especially in ophthalmology.

The Effect of Selective Retina Therapy with Automatic Real-Time Feedback-Controlled Dosimetry for Chronic Central Serous Chorioretinopathy: A Randomized, Open-Label, Controlled Clinical Trial.

This prospective randomized controlled trial evaluated the safety and efficacy of real-time feedback-controlled dosimetry (RFD)-guided selective retina therapy (SRT) in chronic central serous chorioretinopathy (CSC). Forty-four participants with chronic CSC were included and randomly assigned to the control group or SRT group. The SRT laser system with RFD-guidance was applied to cover the entire leakage area. If SRF remained at the 6-week follow-up visit, re-treatment and rescue SRT was performed for the SRT group and crossover group, respectively. The rate of complete resolution of subretinal fluid (SRF), mean SRF height, and mean retinal sensitivity were compared between the two groups at 6-weeks post-treatment. The complete SRF resolution rate in all SRT-treated eyes was evaluated at 12-weeks post-treatment. The rate of complete SRF resolution was significantly higher in the SRT group (63.6%) than in the control group (23.8%) at 6-weeks post-treatment (p = 0.020). The mean SRF height at 6 weeks after SRT was significantly lower in the SRT group (p = 0.041). Overall, SRT-treated eyes showed complete SRF resolution in 70.3% of eyes at 12-weeks post-treatment. RFD-guided SRT was safe and effective to remove SRF in chronic CSC patients during the 3-month follow-up period.

Sodium-Glucose Cotransporter 2 Inhibitors and Risk of Retinal Vein Occlusion Among Patients With Type 2 Diabetes: A Propensity Score-Matched Cohort Study.

OBJECTIVE: To assess the association between use of sodium-glucose cotransporter 2 (SGLT2) inhibitors and retinal vein occlusion (RVO) using data from the National Health Insurance Service in South Korea. RESEARCH DESIGN AND METHODS: We used an active comparator, new user design, and nationwide data from 2014 to 2017. Based on a 1:1 propensity score match, we included 47,369 new users of SGLT2 inhibitors and 47,369 users of other glucose-lowering drugs (oGLDs). In the matched sample, we used the Cox proportional hazards model to estimate hazard ratios (HRs) with 95% CIs for developing RVO. Based on the main outcome, exploratory subgroup analyses were undertaken. RESULTS: During a follow-up of 2.57 years, the incidence rate of RVO was 2.19 and 1.79 per 1,000 person-years in patients treated with SGLT2 inhibitors and oGLDs, respectively. The new use of SGLT2 inhibitors was associated with an increased risk of RVO compared with oGLD use (HR 1.264 [95% CI 1.056, 1.513]). In the subgroup analyses, a significant interaction with SGLT2 inhibitors was observed for age and estimated glomerular filtration rate (eGFR); the HR for RVO was higher in patients aged ≥60 years and those with eGFR <60 mL/min/1.73 m2 than in others. CONCLUSIONS: In a matched cohort study, we found that SGLT2 inhibitors were associated with a significantly increased risk of RVO. Older patients and those with chronic kidney disease were at higher risk for RVO.

Therapeutic Efficacy of Autologous Platelet Concentrate Injection on Macular Holes with High Myopia, Large Macular Holes, or Recurrent Macular Holes: A Multicenter Randomized Controlled Trial.

We aimed to evaluate the anatomical and functional outcomes of pars-plana vitrectomy (PPV) with or without autologous platelet concentrate (APC) injection in patients with recurrent macular holes (MHs), large MHs, or MHs with high myopia. This multicenter, prospective, interventional randomized controlled trial was conducted from March 2017 to April 2020. Participants were randomly allocated to a PPV group or a PPV+APC group. All participants underwent standard 25-gauge PPV, and eyes in the PPV+APC group underwent PPV with intravitreal APC injection before air-gas exchange. A total of 117 patients were enrolled (PPV group: n = 59, PPV+APC group: n = 58). Hole closure was achieved in 47 participants (79.7%) in the PPV group and 52 participants (89.7%) in the PPV+APC group. There were no between-group differences in the anatomical closure rate or functional outcomes including best-corrected visual acuity, metamorphopsia, pattern-reversal visual evoked potential, or Visual Function Questionnaire-25 score. The use of APC injection does not improve the anatomical and functional outcomes of surgery for large MHs, recurrent MHs, or MHs with high myopia. The adjunctive use of APC can be considered in selected cases because it is not inferior to conventional MH surgery, is relatively simple to perform, and is not affected by the surgeon's skill.

Ten-year outcomes after initial management with laser photocoagulation versus intravitreal bevacizumab injection in a pair of identical twins with aggressive posterior retinopathy of prematurity.

PURPOSE: To evaluate the long-term clinical outcomes after initial management with retinal laser photocoagulation (RLP) versus intravitreal bevacizumab (IVB) injection in identical twins with zone Ⅰ aggressive posterior retinopathy of prematurity (AP-ROP). OBSERVATIONS: Identical female twins were born at a gestational age of 28 2/7 weeks, weighing 970 g and 1020 g. The twins were diagnosed with bilateral AP-ROP, referred to a different hospital due to unavilability of a neonatal intensive care unitand received different initial treatments. At a postmenstrual age of 32 6/7 weeks, the first-born infant underwent bilateral IVB (0.313 mg) injection, whereas the second-born infant received bilateral laser photocoagulation on the same day. To treat recurrence, the first-born infant underwent additional bilateral IVB reinjection at 10 weeks post-treatment, while the second-born infant underwent combined bilateral laser photocoagulation and IVB injection at 2 weeks post-treatment.After 10 years, the first-born infant's best corrected visual acuities (BCVAs) of the right and left eyes were 20/20 and 20/50, respectively. Both eyes showed complete retinal vascularization of the peripheral retina and an anatomically normal foveal contour on swept-source optical coherence tomography (SS-OCT). However, the second-born infant's BCVAs of the right and left eyes were 20/50 and 1-m finger-counting, respectively. Both eyes of the second-born infant showed panretinal chorioretinal atrophy due to laser scars, a flattened foveal contour with thin epiretinal membrane in the right eye, and loss of foveal curvature in the left eye on SS-OCT images, 10 years after the initial treatment. Moreover, severe myopia and astigmatism were observed in both eyes of the second-born infant, compared with those of the first-born infant during follow-up. CONCLUSION AND IMPORTANCE: These cases involving identical twins indicated that the effect of initial IVB injection for AP-ROP was superior to that of initial RLP in terms of functional and anatomical outcomes during a 10-year follow-up.

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.

Evaluation of Foveal and Parafoveal Microvascular Changes Using Optical Coherence Tomography Angiography in Type 2 Diabetes Patients without Clinical Diabetic Retinopathy in South Korea.

The aim of this study was to investigate foveal and parafoveal microvascular changes in retinal vascular plexuses in patients with type 2 diabetes mellitus (DM) without clinical diabetic retinopathy (NDR) using optical coherence tomography angiography (OCTA) in South Korea. We included 64 patients in the NDR group and included 48 healthy control subjects for comparison. All subjects underwent ocular examination with visual acuity and wide-field fundus photos. Foveal and parafoveal vessel density and foveal avascular zone (FAZ) area (mm2) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were analyzed. Foveal vessel densities in both the SCP and DCP were decreased in the NDR group compared to the controls (p = 0.034 and 0.001, respectively). Vessel densities in the superior and inferior parafoveae in the DCP were decreased in the NDR group compared to the controls (p = 0.006 and 0.034, respectively). The FAZs of the SCP and DCP were significantly different between the NDR group and the controls (p = 0.003 and 0.001, respectively). The average vessel densities of the SCP and DCP were not correlated with HbA1c, serum creatinine, or the duration of DM in the NDR group. We demonstrated that OCTA can identify early-stage DR before the manifestation of clinically apparent retinopathy in diabetic eyes. Diabetic patients without clinical DR have microvascular alterations (foveal vessel density, parts of the parafovea, and enlarged FAZ) in the SCP and DCP. Our results suggest that OCTA might be a promising tool for early detection of eyes with DR.

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.

Novel Optical Coherence Tomography Parameters as Prognostic Factors for Stage 3 Epiretinal Membranes.

PURPOSE: We aimed to describe the visual prognosis of eyes with ectopic inner foveal layers (EIFLs) after epiretinal membrane (ERM) surgery. METHODS: This retrospective study enrolled patients diagnosed with stage 3 ERM based on the EIFL staging scheme who underwent ERM surgery with a minimum follow-up period of 12 months. Central foveal thickness (CFT), EIFL thickness, and the length of the ellipsoid zone defect were evaluated at baseline and at 1 month, 6 months, and 12 months after surgery based on pre- and postoperative swept-source optical coherence tomography (OCT) images. The association of EIFL thickness and other OCT parameters with pre- and postoperative best-corrected visual acuity (BCVA) was analyzed. RESULTS: Sixty-nine eyes with stage 3 ERMs were analyzed. Preoperative BCVA was correlated with preoperative CFT (r = 0.517, p < 0.001) and preoperative EIFL thickness (r = 0.652, p < 0.001). At 12 months, postoperative BCVA was correlated negatively with preoperative CFT (r = 0.470, p=0.016) and preoperative EIFL thickness (r = 0.582, p=0.004). The improvement in BCVA was not associated with postoperative reduction in CFT (p=0.06), although it was significantly associated with postoperative reduction in EIFL thickness (r = 0.635, p=0.007). CONCLUSIONS: EIFL thickness should be considered a negative prognostic factor for postoperative anatomical and functional recovery in patients with stage 3 ERMs.

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.

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.

Restorative retinal laser therapy: Present state and future directions.

Because of complications and side effects, conventional laser therapy has taken a back seat to drugs in the treatment of macular diseases. Despite this, research on new laser modalities remains active. In particular, various approaches are being pursued to preserve and improve retinal structure and function. These include micropulsing, various exposure titration algorithms, and real-time temperature feedback control of short-pulse continuous wave lasers, and ultra-short-pulse nanosecond lasers. Some of these approaches are at the preclinical stage of development, whereas others are available for clinical use. Cell biology is providing important insights into the mechanisms of action of retinal laser treatment. We outline the technological bases of current laser platforms, their basic science, therapeutic concepts, clinical experience, and future directions for retinal laser 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.