Pigmented Paravenous Retinochoroidal Atrophy: A Case Report Supported by Multimodal Imaging Studies.

Background and Objectives: Pigmented paravenous retinochoroidal atrophy (PPRCA) is a rare disease with bilateral retinal pigment epithelium and choroidal atrophy. We present a case of PPRCA using multimodal imaging studies. Case summary: A 61-year-old female was referred to our department for floaters. Funduscopic examination revealed pigment clumps and grayish lesions along the retinal vein and the peripheral area, bilaterally. She did not have nyctalopia or any other visual symptoms including visual loss. She was diagnosed with pigmented paravenous retinochoroidal atrophy based on the typical findings of fundus. The findings of wide fluorescein angiography (FA), wide indocyanine green angiography (ICGA), fundus autofluorescence (FAF), spectral domain-optical coherence tomography (SD-OCT), optical coherence tomography angiography (OCTA), the visual field (VF) and an electroretinogram (ERG) could help us to confirm the diagnosis. The patient did not have any specific treatment for PPRCA in our study and there was no change in visual acuity and multimodal imaging of both eyes over one year. Conclusions: We report a case of PPRCA and the multimodal imaging of this patient. PPRCA is very rare disease and sometimes it is easy to get confused with other diseases such as retinitis pigmentosa and vasculitis when it comes to diagnosis. Multimodal imaging features of PPRCA will improve our understanding, diagnosis and prediction of the prognosis of this disease.

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.

Surgical Outcomes of Vitrectomy for Macular Hole-induced Retinal Detachment According To Various Surgical Methods: A Multicenter Retrospective Study.

PURPOSE: To investigate the surgical outcomes of vitrectomy for macular hole-induced retinal detachment(MHRD), with respect to the surgical adjunctive method used. METHOD: We performed retrospective multicenter study of patients who underwent vitrectomy for MHRD. The visual/anatomical outcomes after vitrectomy were analyzed. We also analyzed these outcomes according to surgical method and the presence of persistent macular hole after the vitrectomy. RESULT: Thirty-four patients (34 eyes) from 6 hospitals were included in this study. The mean age of the patients was 64.56 ± 12.23 years; 31 patients (91.2%) were female. The mean LogMAR best-corrected visual acuity (BCVA) significantly improved 6 months after vitrectomy (p < .001). Retinal detachment completely improved in 32 eyes (94.1%). The visual prognoses and macular hole closure rates were not different depending on subretinal fluid drainage site. The presence or absence of a persistent macular hole after vitrectomy did not affect the visual outcomes. However, the recurrence of MHRD was significantly higher in eyes with persistent macular holes(p = .015). CONCLUSION: The surgeries to treat MHRD differed in terms of the procedure depending on the surgeons, but the visual outcomes did not differ depending on the surgical adjunctive method employed. There were no differences in the visual prognoses, regardless of whether there was a persistent macular hole; however, recurrence was significantly higher in eyes with persistent macular holes. Therefore, further surgical treatment might be considered for eyes with persistent macular holes after MHRD surgery.

Retinal Laser Therapy Preserves Photoreceptors in a Rodent Model of MERTK-Related Retinitis Pigmentosa.

PURPOSE: We investigated the effects of various retinal laser therapies on preservation of the photoreceptors in an animal model of Mer tyrosine kinase receptor (MERTK)-related retinitis pigmentosa (RP). These modalities included photocoagulation with various pattern densities, selective RPE therapy (SRT), and nondamaging retinal therapy (NRT). METHODS: Laser treatments were performed on right eyes of RCS rats, using one of three laser modalities. For photocoagulation, six pattern densities (spot spacings of 0.5, 1, 1.5, 3, 4, and 5 spot diameters) were delivered in 19-day-old animals, prior to the onset of photoreceptor degeneration, to determine the optimal treatment density for the best preservation of photoreceptors. The left eye was used as control. Rats were monitored for 6 months after treatment using electroretinography, optical coherence tomography, and histology. RESULTS: Photocoagulation resulted in long-term preservation of photoreceptors, manifested morphologically and functionally, with the extent of the benefit dependent on the laser pattern density. Eyes treated with a 1.5 spot size spacing showed the best morphologic and functional preservation during the 6-month follow-up. SRT-treated eyes exhibited short-term morphologic preservation, but no functional benefit. NRT-treated eyes did not show any observable preservation benefit from the treatment. CONCLUSIONS: In a rodent model of MERTK-related RP, pattern photocoagulation of about 15% of the photoreceptors (1.5 spot diameter spacing) provides long-term preservation of photoreceptors in the treatment area. TRANSLATIONAL RELEVANCE: Availability of retinal lasers in ophthalmic practice enables rapid translation of our study to clinical testing and may help preserve the sight in patients with photoreceptor degeneration.

Transplantation of Mature Photoreceptors in Rodents With Retinal Degeneration.

PURPOSE: To demonstrate survival and integration of mature photoreceptors transplanted with the retinal pigment epithelium (RPE). METHODS: Full-thickness retina with attached RPE was harvested from healthy adult rats. Grafts were implanted into two rat models of retinal degeneration, Royal College of Surgeons (RCS) and S334ter-3. Survival of the host and transplanted retina was monitored using optical coherence tomography (OCT) for up to 6 months. The retinal structure and synaptogenesis between the host and transplant was assessed by histology and immunohistochemistry. RESULTS: OCT and histology demonstrated a well-preserved photoreceptor layer with inner and outer segments, while the inner retinal layers of the transplant largely disappeared. Grafts, including RPE, survived better than without and the transplanted RPE appeared as a monolayer integrated with the native one. Synaptogenesis was observed through sprouting of new dendrites from the host bipolar cells and synaptic connections forming with cells of the transplant. However, in many samples, a glial fibrillary acidic protein-positive membrane separated the host retina and the graft. CONCLUSIONS: Presence of RPE in the graft improved the survival of transplanted photoreceptors. Functional integration between the transplant and the host retina is likely to be further enhanced if formation of a glial seal could be prevented. Transplantation of the mature photoreceptors with RPE may be a practical approach to restoration of sight in retinal degeneration. TRANSLATIONAL RELEVANCE: This approach to restoration of sight in patients with photoreceptor degeneration can be rapidly advanced to clinical testing. In patients with central scotoma, autologous transplantation of the peripheral retina can be an option.

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

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

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.

Interferometric mapping of material properties using thermal perturbation.

Optical phase changes induced by transient perturbations provide a sensitive measure of material properties. We demonstrate the high sensitivity and speed of such methods, using two interferometric techniques: quantitative phase imaging (QPI) in transmission and phase-resolved optical coherence tomography (OCT) in reflection. Shot-noise-limited QPI can resolve energy deposition of about 3.4 mJ/cm2 in a single pulse, which corresponds to 0.8 °C temperature rise in a single cell. OCT can detect deposition of 24 mJ/cm2 energy between two scattering interfaces producing signals with about 30-dB signal-to-noise ratio (SNR), and 4.7 mJ/cm2 when SNR is 45 dB. Both techniques can image thermal changes within the thermal confinement time, which enables accurate single-shot mapping of absorption coefficients even in highly scattering samples, as well as electrical conductivity and many other material properties in biological samples at cellular scale. Integration of the phase changes along the beam path helps increase sensitivity, and the signal relaxation time reveals the size of hidden objects. These methods may enable multiple applications, ranging from temperature-controlled retinal laser therapy or gene expression to mapping electric current density and characterization of semiconductor devices with rapid pump-probe measurements.

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.

Sleep and diabetic retinopathy.

PURPOSE: To investigate the association between sleep duration and diabetic retinopathy (DR). METHODS: A population-based cross-sectional study using a nation-wide, systemically stratified, multistage, clustered sampling method included a total of 1670 subjects aged ≥40 years with diabetes who participated in the Korean National Health and Nutrition Examination Survey during 2008-2012. All participants performed standardized interviews, including self-reported sleep duration, and comprehensive ophthalmic examinations. Seven standard retinal fundus photographs were obtained from both eyes after pupil dilatation. Diabetic retinopathy (DR) was graded and classified as any DR and vision-threatening DR. Participants were stratified into men and women. RESULTS: The mean sleep duration was 6.71 hr/day. In men, adjusted OR of any DR was 1.88 [95% confidence interval (OR), 1.01-3.59] in those with ≤5 hr sleep, and 2.19 (95% CI, 1.01-4.89) in those with ≥9 hr sleep, compared to in subjects with 6-8 hr sleep, after adjusting for potential confounders including age, body mass index (BMI), diabetes duration, fasting glucose level, haemoglobin A1c levels and hypertension. In women, however, no significant association between sleep duration and DR was found. The vision-threatening DR was not significantly associated with sleep duration in either men or women. CONCLUSIONS: Short and long sleep was associated with high prevalence of DR in men. Sleep deprivation may be involved in the pathogenesis of DR development.

The Antiangiogenic Effects of Gold Nanoparticles on Experimental Choroidal Neovascularization in Mice.

Purpose: The purpose of this study was to evaluate the antiangiogenic effect of gold nanoparticles (AuNPs) on experimental choroidal neovascularization (CNV) in mice. Methods: Choroidal neovascularization was induced by rupturing the Bruch's membrane using laser photocoagulation in C57BL/6 mice. The following day, intravitreal injections of AuNPs were administered. The control group received PBS injection of the same volume. Two weeks after laser injury, CNV lesions were evaluated by examination of choroidal flat-mounts using fluorescein-labeled dextran and immunofluorescence staining with isolectin B4. The effects of AuNPs on endothelial cell tube formation, proliferation, and cytotoxicity were evaluated using human umbilical vein endothelial cells (HUVECs) or human RPE cells. The activity of extracellular signal-regulated kinase (ERK)1/2, protein kinase B (Akt), and focal adhesion kinase (FAK) signaling pathways was also analyzed. Results: The AuNPs reduced the extent of CNV. Mice treated with intravitreal AuNPs injections exhibited a 67.9% reduction in the extent of CNV lesions compared with the control group (P < 0.001). The size of the isolectin B4-labeled area was also significantly smaller in AuNP-treated groups compared with the control group (P < 0.001). Gold nanoparticles decreased vascular endothelial growth factor-induced HUVEC tube formation and proliferation but showed no RPE cell toxicity with the treatment doses administered. The phosphorylation of ERK1/2, Akt, and FAK in HUVECs was suppressed by AuNPs. Conclusions: Gold nanoparticles can inhibit laser-induced CNV in mice and may have an indication for the treatment of CNV.

Differential Effects of Bevacizumab, Ranibizumab, and Aflibercept on the Viability and Wound Healing of Corneal Epithelial Cells.

PURPOSE: This study compared the effects of 3 antivascular endothelial growth factor (VEGF) agents (bevacizumab, ranibizumab, and aflibercept) on corneal epithelial cell viability and wound healing using human corneal epithelial cells (HCECs). METHODS: To determine the cytotoxic effects of anti-VEGF agents on HCECs, HCEC viability was determined at various concentrations of these agents. An in vitro migration assay was used to investigate the migration of HCECs treated with 3 anti-VEGF agents. The protein level of extracellular signal-regulated kinase was used to evaluate the effect of anti-VEGF treatment on cell proliferation. The protein levels of p38 mitogen-activated protein kinase (MAPK) were analyzed by Western blotting to investigate cell migration. RESULTS: After 24 or 48 h of exposure, aflibercept treatment showed no apparent effect on cell viability; however, bevacizumab and ranibizumab treatment decreased cell viability at high concentrations (1 and 2 mg/mL). A migration assay showed that HCEC migration was different among the 3 anti-VEGF treatment groups. Bevacizumab significantly delayed HCEC migration. Western blotting showed that bevacizumab treatment decreased the expression levels of phosphorylated p38 MAPK. CONCLUSIONS: Bevacizumab, the most widely used and investigated anti-VEGF agent, decreased epithelial cell migration and viability. Anti-VEGF agents other than bevacizumab might therefore be better for treating corneal neovascularization complicated with epithelial defects.

Melissa Officinalis L. Extracts Protect Human Retinal Pigment Epithelial Cells against Oxidative Stress-Induced Apoptosis.

BACKGROUND: We evaluated the protective effect of ALS-L1023, an extract of Melissa officinalis L. (Labiatae; lemon balm) against oxidative stress-induced apoptosis in human retinal pigment epithelial cells (ARPE-19 cells). METHODS: ARPE-19 cells were incubated with ALS-L1023 for 24 h and then treated with hydrogen peroxide (H2O2). Oxidative stress-induced apoptosis and intracellular generation of reactive oxygen species (ROS) were assessed by flow cytometry. Caspase-3/7 activation and cleaved poly ADP-ribose polymerase (PARP) were measured to investigate the protective role of ALS-L1023 against apoptosis. The protective effect of ALS-L1023 against oxidative stress through activation of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) was evaluated by Western blot analysis. RESULTS: ALS-L1023 clearly reduced H2O2-induced cell apoptosis and intracellular production of ROS. H2O2-induced oxidative stress increased caspase-3/7 activity and apoptotic PARP cleavage, which were significantly inhibited by ALS-L1023. Activation of the PI3K/Akt pathway was associated with the protective effect of ALS-L1023 on ARPE-19 cells. CONCLUSIONS: ALS-L1023 protected human RPE cells against oxidative damage. This suggests that ALS-L1023 has therapeutic potential for the prevention of dry age-related macular degeneration.

Serum 25-Hydroxyvitamin D Levels and Dry Eye Syndrome: Differential Effects of Vitamin D on Ocular Diseases.

PURPOSE: To investigate associations between serum 25-hydroxyvitamin D levels and dry eye syndrome (DES), and to evaluate the differential effect of vitamin D on ocular diseases including age-related macular disease (AMD), diabetic retinopathy (DR), cataract, and DES. METHODS: A total of 16,396 participants aged >19 years were randomly selected from the Korean National Health and Nutrition Examination Survey. All participants participated in standardized interviews, blood 25-hydroxyvitamin D level evaluations, and comprehensive ophthalmic examinations. DES was defined by a history of clinical diagnosis of dry eyes by a physician. The association between vitamin D and DES was compared to the associations between vitamin D and AMD, DR, cataract, and DES from our previous studies. RESULTS: The odds of DES non-significantly decreased as the quintiles of serum 25-hydroxyvitamin D levels increased (quintile 5 versus 1, OR = 0.85, 95%CI: 0.55-1.30, P for trend = 0.076) after adjusting for potential confounders including age, sex, hypertension, diabetes, smoking status, and sunlight exposure times. The relative odds of DES (OR = 0.70, 95% CI: 0.30-1.64) and cataract (OR = 0.76, 95% CI: 0.59-0.99) were relatively high, while those of DR (OR = 0.37, 95% CI: 0.18-0.76) and late AMD (OR = 0.32, 95% CI: 0.12-0.81) were lower in men. CONCLUSIONS: The present study does not support an association between serum 25-hydroxyvitamin D levels and DES. The preventive effect of serum 25-hydroxyvitamin D may be more effective for DR and late AMD than it is for cataract and DES.

Functional and morphological evaluation of blue light-emitting diode-induced retinal degeneration in mice.

PURPOSE: The purpose of this study was to evaluate a retinal degeneration (RD) model induced by exposing mice to a blue light-emitting diode (LED), which led to photoreceptor cell death. METHODS: RD was induced in BALB/c mice by exposure to a blue LED (460 nm) for 2 hours. Retinal function was examined using scotopic electroretinography (ERG). Histopathological changes were assessed by hematoxylin and eosin (H&E) staining and electron microscopy. Apoptotic cell death was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. In addition, retinal inflammation and oxidative stress were evaluated by immunohistochemistry with anti-glial fibrillary acidic protein (GFAP) and anti-8-hydroxy-2'-deoxyguanosine (8-OHdG), respectively. RESULTS: Scotopic ERG showed that blue LED exposure resulted in a decrease in both a-waves and b-waves in mice retinas in an illuminance-dependent manner. H&E, TUNEL assay, and electron microscopy revealed massive photoreceptor cell death by apoptosis in the central region of the retina. Retinal stress and inflammation were detected by increased expression of GFAP and by electron microscopy findings demonstrating microglia infiltration in the outer nuclear layer and subretinal space. In addition, increased labeling of 8-OHdG was observed in the retinas from blue LED exposure. CONCLUSIONS: These results suggest that blue LED-induced RD may be a useful animal model in which to study the pathogenesis of RD, including age-related macular degeneration, and to evaluate the effects of new therapeutic agents prior to clinical trials, where oxidative stress and inflammation are the underlying RD mechanisms.

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.

Selective Retina Therapy in Patients With Chronic Central Serous Chorioretinopathy: A Pilot Study.

We evaluated visual outcomes, changes of maximum macular thickness (MMT) and subretinal fluid (SRF), and safety in patients with chronic central serous chorioretinopathy (CSC) after treatment with selective retina therapy (SRT). Retrospective cohort study of patients with chronic CSC presenting to a university-based hospital from January 2014 through January 2015 was conducted. A total of 12 eyes of 12 patients with chronic CSC lasting for at least 3 months was recruited. The follow-up period ranged from 3 to 12 months. Following evaluation of test spots at temporal arcades, SRT (Q-switched neodymium-doped yttrium lithium fluoride [Nd:YLF] laser; wavelength, 527 nm, pulse duration, 1.7 microsececond) was applied to the surrounding areas of leakage observed on fluorescein angiogram and/or pigment epithelial detachment (PED). Changes in best-correct visual acuity (BCVA), MMT, and SRF and macular sensitivity (MS) by microperimetry (MP) were evaluated. Eyes received treatment in a mean of 3.83 spots at the pulse energy of 65 to 90 µJ. Mean BCVA (logMAR) improved from 0.23 ±â€Š0.12 at baseline to 0.14 ±â€Š0.13 at 3 months. MMT decreased from 341.4 ±â€Š85.5 µm at baseline to 236.0 ±â€Š57.9 µm at 3 months. SRF completely resolved in 75% (9 eyes) at 3 months. Large PEDs (2 eyes) were flattened at 3 months. Retreatment was performed in 4 eyes. MP showed no evidence of scotoma around SRT-treated lesions. SRT treatment targeting the surrounding area of leakage point showed favorable visual and structural outcomes in chronic CSC patients without the risk of scotoma.

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.

A Comparative Study of Retinal Function in Rabbits after Panretinal Selective Retina Therapy versus Conventional Panretinal Photocoagulation.

Purpose. This study evaluates functional changes in electroretinographic findings after selective retina therapy (SRT) compared to panretinal photocoagulation (PRP) in rabbits. Methods. The right eyes of 12 Chinchilla rabbits received 200 laser treatment spots. The right eyes of six rabbits received SRT (SRT group), whereas the other six animals were treated using PRP on the right eye (PRP group). The eyes were investigated using full-field ERG 1 hour and 3 weeks after treatment. Histologic exam to assess the tissue response of lasers was performed on 3 weeks. Results. No significant changes in the mean ROD or CR b-wave amplitudes of the SRT lesions were evident, compared to baseline, 1 h after laser treatment (p = 0.372 and 0.278, resp.). In addition, the OPs and 30 Hz flickers of the SRT lesions were not significantly altered (p = 0.17 and 0.243, resp.). At 3 weeks, similar results were found. Comparing the two groups, the ROD b-wave amplitude was reduced in the PRP and SRT groups to 60.04 ± 4.2% and 92.32 ± 6.43% of baseline (p < 0.001). Histologically, there was no visible photoreceptor alterations on week 3. Conclusions. SRT in rabbit eyes induced less functional loss than PRP in both rod-mediated retinal function and cone-mediated retinal function. In addition, SRT irradiated eyes had no functional loss compared to its control.

Effects of Granulocyte-Macrophage Colony-Stimulating (GM-CSF) Factor on Corneal Epithelial Cells in Corneal Wound Healing Model.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that activates granulocyte and macrophage cell lineages. It is also known to have an important function in wound healing. This study investigated the effect of GM-CSF in wound healing of human corneal epithelial cells (HCECs). We used human GM-CSF derived from rice cells (rice cell-derived recombinant human GM-CSF; rhGM-CSF). An in vitro migration assay was performed to investigate the migration rate of HCECs treated with various concentrations of rhGM-CSF (0.1, 1.0, and 10.0 µg/ml). MTT assay and flow cytometric analysis were used to evaluate the proliferative effect of rhGM-CSF. The protein level of p38MAPK was analyzed by western blotting. For in vivo analysis, 100 golden Syrian hamsters were divided into four groups, and their corneas were de-epithelialized with alcohol and a blade. The experimental groups were treated with 10, 20, or 50 µg/ml rhGM-CSF four times daily, and the control group was treated with phosphate-buffered saline. The corneal wound-healing rate was evaluated by fluorescein staining at the initial wounding and 12, 24, 36, and 48 hours after epithelial debridement. rhGM-CSF accelerated corneal epithelial wound healing both in vitro and in vivo. MTT assay and flow cytometric analysis revealed that rhGM-CSF treatment had no effects on HCEC proliferation. Western blot analysis demonstrated that the expression level of phosphorylated p38MAPK increased with rhGM-CSF treatment. These findings indicate that rhGM-CSF enhances corneal wound healing by accelerating cell migration.