Comparison of surgical outcomes of macular telangiectasia type 2 associated macular hole with idiopathic macular hole: A tertiary center review.

PURPOSE: To assess the longitudinal surgical outcomes of macular telangiectasia type 2 macular hole (MacTel-MH) and compare them with those of idiopathic MH. METHODS: This retrospective, single-tertiary center study included patients who underwent MH surgery between January 2015 and September 2023. Patients with characteristic optical coherence tomography (OCT) findings of MacTel in both eyes or those who underwent fluorescence angiography were classified as having MacTel MH. Baseline and postoperative best-corrected visual acuity and OCT parameters were reviewed. RESULTS: Totally, 27 and 243 eyes with MacTel and idiopathic MH, respectively, were included. MH closure rate was better achieved in idiopathic than in MacTel MH group at 2 years postoperatively. Temporal recovery of ellipsoid zone and external limiting membrane was more prominent in MacTel than in idiopathic MH group. Statistically significant visual acuity improvement was seen between 3 months and 2 years postoperatively in MacTel MH group. CONCLUSION: To the best of our knowledge, this is the first study to analyze the surgical outcomes of MacTel MH in both anatomical and functional aspects and compare them with patients with idiopathic MH. Postoperative microglia change would have affected the restoration of outer retinal layer of patients; however, further studies are needed for clarification.

Choroidal and retinal vascular changes in HLA-B27-associated anterior uveitis.

PURPOSE: To quantitatively analyze choroidal and retinal vascular changes in HLA-B27-associated anterior uveitis. STUDY DESIGN: A retrospective study. METHODS: Medical records of 51 eyes with unilateral HLA-B27-associated anterior uveitis, their fellow eyes and 47 sex and age-matched healthy eyes were retrospectively reviewed. Their choroidal and retinal vasculature were analyzed using swept-source (SS) optical coherence tomography (OCT) and OCT angiography (OCTA) scans. RESULTS: Deep capillary plexus (DCP) vessel density (VD) (p < 0.001), choroidal vascularity index (CVI) (p = 0.012), and choriocapillary flow deficit (CCFD) (p < 0.001) of uveitic and fellow eye group were significantly higher than those of control group. On the contrary, superficial capillary plexus (SCP) VD (p < 0.001) of uveitic and fellow eye group were significantly lower than of control group. The vascular parameters of uveitis and fellow eye group showed no significant difference between uveitic and resolution period. CONCLUSION: Certain choroidal and retinal vascular parameters were significantly changed in both HLA-B27-associated anterior uveitis without posterior segment involvement and the quiet fellow eyes, suggesting their possible effects as a systemic inflammatory disorder.

AIBP: A New Safeguard against Glaucomatous Neuroinflammation.

Glaucoma is a group of ocular diseases that cause irreversible blindness. It is characterized by multifactorial degeneration of the optic nerve axons and retinal ganglion cells (RGCs), resulting in the loss of vision. Major components of glaucoma pathogenesis include glia-driven neuroinflammation and impairment of mitochondrial dynamics and bioenergetics, leading to retinal neurodegeneration. In this review article, we summarize current evidence for the emerging role of apolipoprotein A-I binding protein (AIBP) as an important anti-inflammatory and neuroprotective factor in the retina. Due to its association with toll-like receptor 4 (TLR4), extracellular AIBP selectively removes excess cholesterol from the plasma membrane of inflammatory and activated cells. This results in the reduced expression of TLR4-associated, cholesterol-rich lipid rafts and the inhibition of downstream inflammatory signaling. Intracellular AIBP is localized to mitochondria and modulates mitophagy through the ubiquitination of mitofusins 1 and 2. Importantly, elevated intraocular pressure induces AIBP deficiency in mouse models and in human glaucomatous retina. AIBP deficiency leads to the activation of TLR4 in Müller glia, triggering mitochondrial dysfunction in both RGCs and Müller glia, and compromising visual function in a mouse model. Conversely, restoring AIBP expression in the retina reduces neuroinflammation, prevents RGCs death, and protects visual function. These results provide new insight into the mechanism of AIBP function in the retina and suggest a therapeutic potential for restoring retinal AIBP expression in the treatment of glaucoma.

Long-term visual prognosis and characteristics of recurrent retinal detachment after silicone oil removal.

PURPOSE: Silicone oil (SO) is commonly used for tamponade purposes in retinal detachment (RD) surgery, but the long-term visual prognosis after removal of the oil, and in particular, what is known about the recurrence of RD after SO removal, remains unclear. The purpose of this study is to evaluate the long-term vision prognosis after SO removal, and to understand the frequency and characteristics of RD recurrence. METHODS: We retrospectively reviewed the medical charts of 1017 eyes of patients with a diagnosis of RD who had a pars plana vitrectomy with SO tamponade between January 2009 and December 2018. Best-corrected visual acuity (BCVA) was obatained before and after vitrectomy and also at the last visit. After SO removal, the group who showed improvement in visual acuity and the group who did not were compared. The anatomical results were compared between the group in which the retina was detached again after SO removal and the group in which the retina was not detached. To determine whether the duration of SO tamponade affects RD recurrence, further analysis was performed by dividing subgroups according to SO tamponade duration. RD recurrence, visual acuity, SO tamponade period were investigated. RESULTS: Mean follow-up period was 56.65 ± 72.02 months. An average SO tamponade period was 6.68 ± 11.39 months. The average logMAR BCVA was 1.75 ± 0.91 before SO injection, 1.60 ± 0.75 before SO removal and 1.29 ± 0.96 after the removal. After SO removal, 926 of the 1017 (91.1%) patients had well attached retina without recurrence. There was no significant difference in visual acuity before SO removal in re-detachment group compared to no re-detachment group, but visual acuity of re-detachment group was worse than no re-detachment group after SO removal (p<0.001). The SO tamponade period in the group with improved vision after SO removal was 5.09 ± 9.87 months, and the period was significantly shorter than the 9.09 ± 13.05 months in the group not showing vision recovery (p = 0.005). The occurrence of corneal opacity was significantly higher in the group with SO over 6 months, than those of the two groups with SO tamponade duration of less than 3 months and between 3 and 6 months (p = 0.038). The longest tamponade group showed the worst final vision after SO removal (p<0.001). CONCLUSION: The prognosis for final vision is generally good when performing surgery using SO in RD, but considering the complications that arise after surgery, long-term retention of SO is not recommended and the timing of SO removal should be considered.

Choroidal vascularity index change in macular telangiectasia type 2.

PURPOSE: To analyze choroidal structure using subfoveal choroidal thickness (SFCT) and choroidal vascularity index (CVI) in Macular Telangiectasia (MacTel) type 2. METHODS: Medical records of 43 eyes with MacTel type 2 and 30 sex and age-matched healthy eyes were retrospectively reviewed. Their SFCT and CVI were measured using the SS-OCT scan passing through the central fovea and image binarization. The difference in baseline SFCT and CVI from each group and their yearly changes up to second year of follow up were analyzed. The baseline characteristics of the groups were also compared. RESULTS: The baseline characteristics, including CVI and SFCT, of the MacTel group and the control group were not significantly different, except for BCVA. The mean CVI of MacTel group were 64.59 ± 2.92%, 63.76 ± 2.67%, and 62.97 ± 2.74% (p < 0.001) whereas that of control group were 63.33 ± 2.45%, 63.04 ± 2.46%, and 63.43 ± 2.25% (p = 0.636) at baseline, 1 and 2 years, respectively. The mean SFCT of MacTel group were 324.65 ± 89.65µm, 326.14 ± 93.11µm, and 322.65 ± 91.77µm (p = 0.436), whereas that of control group were 304.30 ± 51.86 µm, 300.86 ± 52.64µm, and 298.55 ± 53.71µm (p = 0.275) at baseline, 1 and 2 years, respectively. CONCLUSION: CVI decreases at a faster rate in MacTel type 2 in comparison with healthy subjects. This may suggest possible choroidal involvement in the progression of MacTel type 2.

CLINICAL FEATURES OF INTRAVITREAL DEXAMETHASONE IMPLANTATION IN VITRECTOMIZED EYES OF PATIENTS WITH DIABETIC MACULAR EDEMA.

PURPOSE: To identify the clinical outcomes of intravitreal dexamethasone implantation (IVD) in previously vitrectomized eyes of patients with diabetic macular edema. METHOD: We performed a retrospective observational study. We recorded central subfield thickness, best-corrected visual acuity, and intraocular pressure up to 12 months after IVD implant placement. We compared the duration of IVD action, intraocular pressure trends, and the prevalence of ocular hypertension after the first IVD treatment of nonvitrectomized and vitrectomized eyes. We also compared the central subfield thickness, best-corrected visual acuity, number of IVD treatments, and prevalence of ocular hypertension between the 2 groups after 12 months. RESULTS: We found no significant between-group differences in the central subfield thickness, best-corrected visual acuity, or the prevalence of ocular hypertension during treatment. However, the duration of action of the first IVD treatment was significantly shorter in vitrectomized eyes, and these eyes required more IVD treatments during the 12-month follow-up period. The maximal average intraocular pressure was observed at 2 months after the first IVD treatment in the nonvitrectomized group, but 1 month after the first IVD treatment in the vitrectomized group. CONCLUSION: These findings suggest that the IVD pharmacokinetics and pharmacodynamics differ between vitrectomized and nonvitrectomized eyes. Nevertheless, given the relatively long-lasting effectiveness of the treatment and the good clinical results, consecutive IVD treatments may be beneficial for patients with diabetic macular edema with previously vitrectomized eyes.

Long-Term Analysis of Clinical Features and Treatment Outcomes of Inflammatory Choroidal Neovascularization.

PURPOSE: To investigate the long-term clinical features and treatment outcomes of patients with inflammatory choroidal neovascularization (CNV) treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF). DESIGN: Retrospective, interventional, consecutive case series. METHODS: Sixty-five eyes of 65 patients with inflammatory CNV treated with anti-VEGF injections and followed up at least 12 months were included. Retrospective chart review was conducted at a single tertiary referral center. RESULTS: Study participants were followed up for 60.6 ± 42.8 (range, 16-160) months. Mean age was 33.4 ± 10.8 years, and mean refractive error was -3.94 ± 1.35 D in spherical equivalent. Final best-corrected visual acuity (BCVA) was 0.21 ± 0.20 logMAR after treatment. Patients were treated with bevacizumab (76.9%), ranibizumab (4.6%), aflibercept (3.1%), and drug combinations (15.4%). Systemic corticosteroid or immunosuppressant use was not correlated with visual outcome, required number of anti-VEGF injections, and recurrence. Commonly occurring optical coherence tomography (OCT) features included ellipsoid zone disruption, choroidal hypertransmission, retinal pigment epithelium atrophy or absence (RPEA), intraretinal hyperreflective foci (HRF), choroidal vessel engorgement, focal choroidal excavation, and irregular vascular loops (on OCT angiography). RPEA after treatment (ß = 0.238, P = .036) and BCVA (ß = 0.267, P = .029) showed significant correlation with final BCVA. A total of 28 patients (43.1%) experienced recurrence; intraretinal HRF after treatment was the single risk factor for recurrence (odds ratio = 2.712, P = .031). CONCLUSIONS: Inflammatory CNV recurrence showed higher rates over time after anti-VEGF treatment than previously reported, even though the overall visual outcome was good. Baseline BCVA and RPEA after treatment are significant predictors for visual outcome. Intraretinal HRF after anti-VEGF treatment suggests the potential risk of recurrence.

The effect of phacoemulsification performed with vitrectomy on choroidal vascularity index in eyes with vitreomacular diseases.

This study evaluated the effects of cataract surgery combined with pars plana vitrectomy (ppV) on choroidal vascularity index (CVI) in eyes with epiretinal membrane (ERM) and full thickness macular hole (FTMH). Medical records of 132 eyes with ERM or FTMH were retrospectively reviewed and classified into a ppV group and a ppV combined with cataract surgery group (phaco + ppV group). The CVI were measured at baseline, 1, 3 and 6 months after the surgery, using the selected swept-source (SS) optical coherence tomography (OCT) scan passing through the central fovea, which was then segmented into luminal and stromal area by image binarization. The mean CVI of phaco + ppV group were 61.25 ± 1.97%, 61.66 ± 1.81%, and 62.30 ± 1.92% at baseline, 1 and 3 months, respectively (p < 0.001). The mean CVI of ppV group were 62.69 ± 1.92%, 62.03 ± 1.51%, and 61.45 ± 1.71% at baseline, 1 and 3 months, respectively (p < 0.001). The final CVI were measured at 6 months and compared with the baseline CVI. The mean CVI of phaco + ppV group were 61.21 ± 1.99% at baseline and 60.68 ± 2.02% at 6 months (p < 0.001). The mean CVI of ppV group were 62.93 ± 1.70% at baseline and 61.77 ± 1.74% at 6 months (p < 0.001). Vitrectomy significantly decreases CVI in vitreomacular diseases possibly due to the removal of vitreomacular traction or postoperative oxygenation change in the eye. On the contrary, combined surgery of vitrectomy and cataract surgery significantly increases CVI in the early stage of postoperative period, which suggests choroidal vascular dilatation or congestion due to postoperative inflammation. Although the CVI were measured lower than the baseline in the end, more thorough inflammation control may be essential after combined surgery.

Characteristics of retinal detachment associated with atopic dermatitis.

BACKGROUND: To examine the characteristics of rhegmatous retinal detachment (RRD) associated with atopic dermatitis. METHOD: Medical records of 2257 patients who underwent RD surgery at this clinic between 2008 and 2018 were retrospectively reviewed. Among them, 61 patients who were diagnosed as AD were assigned into the experimental group and 100 patients who did not have AD were randomly selected and assigned into the control group. Demographics, characteristics of detachment, initial operative method, and prognosis after surgery were investigated as main outcomes. Additionally, in pseudophakic RD patients, the period between the cataract surgery and onset of RD was measured. RESULT: Postoperative VA and prognosis were significantly worse and bilateral involvement of RD was more common in the atopy group than in the control group. (P value = 0.005, 0.001 each) Characteristics of retinal breaks were different between the two groups. Additionally, the risk of developing RD within 1 year after cataract surgery was significantly higher in pseudophakic patients of the atopic group than in the control group. (P value = 0.013) However, there was no significant difference in mean preoperative VA or refractive index between the two groups. CONCLUSION: Our results show that in atopic patients, RD occurs at a young age with different characteristics compared to non-atopic patients. Atopic RD has a poor visual prognosis. Thus, it requires careful management. Furthermore, the risk of developing RD within 1 year after cataract surgery is higher in atopic patients. Therefore, it is important to perform regular and extensive check-up after cataract surgery for atopic patients.

Clinical course after the onset of choroidal neovascularization in eyes with central serous chorioretinopathy.

ABSTRACT: Chronic central serous chorioretinopathy (CSC) can be complicated with choroidal neovascularization (CNV); however, the timing of its occurrence and its clinical significance are not well understood. This study aimed to observe the time of choroidal neovascularization detection after CSC diagnosis and determine whether clinical features and prognosis differed in patients with chronic CSC or age-related retinal degeneration.In this retrospective study, medical records of CSC patients complicated with CNV who visited Seoul St. Mary's hospital of Korea between October 2009 and December 2020 were reviewed. The presence of CNV was determined using fluorescein, indocyanine green, or optical coherent tomography angiography (OCTA). Based on the patients' medical records, we observed the change of clinical pattern, best-corrected visual acuity (BCVA) and central macular thickness (CMT) at CNV detection and at 6 months, 1 year, 3 years, and 5 years following CNV detection.Thirty eyes of 30 patients (male: female ratio of 13:17) were enrolled. Mean age at diagnosis of CSC was 54.0 ±â€Š8.5 years (mean ±â€Šstandard deviation). On average, CNV was detected 1.65 ±â€Š2.30 years after the diagnosis of CSC. The mean CMT was significantly decreased at 6 months, 1 year, and 3 years after choroidal neovascularization detection (P < .001, P < .001, P = .001 respectively). BCVA tend to improve after CNV detection, but there was no statistical significance at 6 months, 1 year, 3 years, and 5 years (all with P > .05). There were no clinical findings suggesting age-related macular degeneration such as intraretinal, subretinal hemorrhage or drusen in any of the case during follow-up. None of the subjects had severe visual acuity loss of 1.0 logarithm of the minimum angle of resolution (logMAR) (20/200 Snellen equivalent) or greater. Among the subjects, 6 patients (20%) did not require any treatment during observation, while 24 other patients required anti-vascular endothelial growth factor (anti-VEGF) or photodynamic therapy. At the last visit, 22 patients (73.3%) remained stable for more than 6 months, without subretinal fluid recurrence.Choroidal neovascularization was detected earlier than previously reported. There was no rapid deterioration of visual acuity or clinical features even after CNV detection.

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.

Unaffected fellow eye neovascularization in patients with type 3 neovascularization: Incidence and risk factors.

PURPOSE: To evaluate the incidence and risk factors of neovascularization in unaffected fellow eyes of patients diagnosed with type 3 neovascularization in Korea. METHODS: This retrospective study included 93 unaffected fellow eyes of 93 patients diagnosed with type 3 neovascularization. For initial type 3 neovascularization diagnosis, optical coherence tomography and angiography were conducted. These baseline data were compared between patients with and without neovascularization in their fellow eyes during the follow-up period. RESULTS: The mean follow-up period was 66.1±31.1 months. Neovascularization developed in 49 (52.8%) fellow eyes after a mean period of 29.5±19.6 months. In the fellow eye neovascularization group, the incidence of soft drusen and reticular pseudodrusen was significantly higher than that in the non-neovascularization group (83.7% vs. 36.5%, p<0.001; 67.3% vs. 40.9%, p = 0.017, respectively), but the choroidal vascularity index (CVI) showed a significantly lower value (60.7±2.0% vs. 61.7±2.5%; p = 0.047). The presence of reticular pseudodrusen was related with the duration from baseline to development of fellow eye neovascularization (p = 0.038). CONCLUSION: Neovascularization developed in 52.8% of unaffected fellow eyes. The presence of soft drusen, reticular pseudodrusen, and lower CVI values can be considered risk factors of neovascularization in unaffected fellow eyes of patients with type 3 neovascularization. The lower CVI values suggest that choroidal ischemic change may affect the development of choroidal neovascularization in these patients.

C-reactive protein/albumin ratio as an indicator of disease activity in Behçet's disease and human leukocyte antigen-B27-associated uveitis.

PURPOSE: To explore the role of systemic inflammatory markers as indicators of acute exacerbation of chronic diseases and disease activity in uveitis. METHODS: This study included 50 patients with Behçet's disease (BD)-associated uveitis and 52 patients with human leukocyte antigen-B27 (HLA-B27)-associated uveitis. Laboratory tests were conducted to measure complete blood count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), CRP/albumin ratio (CAR), neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) during the uveitis phase and after resolution. The results measured during the two phases were assessed and compared. RESULTS: The mean age of the participants was 41.4 ± 10.8 years; 68.6% of the patients were male. In both groups, ESR, CRP, and CAR were significantly higher during the uveitic phase (P < .001). However, the white blood cell count, albumin, NLR, and PLR measured during the uveitic phase and after resolution did not vary significantly (P > .05). ESR and CAR were correlated with the severity of intraocular inflammation. The area under the curve (AUC) of CAR, which was used to predict the presence of uveitis, was 0.801 (95% CI, 0.741-0.861); this value is strong compared with those of other inflammatory biomarkers. CONCLUSIONS: CAR is correlated with the severity of intraocular inflammation in BD- and HLA-B27-associated uveitis. Furthermore, CAR appears to be a useful marker of disease activity for uveitis and is the most sensitive marker for discriminating the presence of acute uveitis in patients who have chronic uveitis as a symptom of BD- and HLA-B27-associated diseases.

OPTICAL COHERENCE TOMOGRAPHY BIOMARKERS FOR REDUCTION OF DRUSENOID PIGMENT EPITHELIUM DETACHMENT.

PURPOSE: To identify the optical coherence tomography biomarkers that can collectively predict the probability of collapse or reduction of drusenoid pigment epithelium detachment (PED). METHODS: This consecutive observational case series reviewed the clinical data of 24 eyes with non-neovascular drusenoid PED. Among the study population, 17 eyes showed collapse or reduction of drusenoid PED. The mean follow-up duration was 44.8 ± 24.6 months. Optical coherence tomography-derived parameters were analyzed at baseline, at the last available visit before reduction of PED, at the first available visit after reduction of PED, and at the final visit. RESULTS: The mean subfoveal choroidal thickness showed a significant decrease after PED reduction and at the most recent visit (P = 0.015). Migration of retinal pigment epithelium cells was detected in 15 (88.2%) after PED reduction; however, there was no significance in the frequency of migration of retinal pigment epithelium cells at each time point (P = 0.392). Non-neovascular subretinal fluid was detected in 7 (41.2%) before PED reduction, 2 (11.8%) after PED reduction, and 2 (11.8%) at the final visit. Interestingly, subretinal fluid appeared more frequently just before reduction of PED (P = 0.029). CONCLUSION: We found evidence of non-neovascular subretinal fluid and choroidal thinning before reduction in PED. This finding might be useful for detection and prediction of the progression of drusenoid PED.

Prognostic factors of cytomegalovirus retinitis after hematopoietic stem cell transplantation.

PURPOSE: To identify the visual prognostic factors in patients with cytomegalovirus (CMV) retinitis after hematopoietic stem cell transplantation (HSCT). METHODS: This retrospective cohort study included 4241 patients who underwent HSCT from April 1, 2010 to March 31, 2019 at Seoul St. Mary's Hospital. Of them, 1063 patients presented CMV viremia, and 67 patients (93 eyes) were diagnosed with CMV retinitis. We enrolled 66 patients (91 eyes). The main outcomes included the initial best-corrected visual acuity (BCVA), BCVA at the diagnosis of retinitis and last visit, involved retinal zone, peak CMV DNA levels in the peripheral blood and aqueous humor, time between HSCT and the diagnosis of retinitis, time between the diagnosis of viremia and retinitis, complications, recurrence, survival, and so on. RESULTS: The mean BCVA (logarithm of the minimum angle of resolution) values before HSCT, at the time of retinitis diagnosis, and at the last visit were 0.041 ± 0.076, 0.262 ± 0.529, and 0.309 ± 0.547, respectively. Multiple regression analysis revealed that the involved zone (P = 0.001), time between HSCT and retinitis diagnosis (P = 0.019), and survival status (P = 0.001) were associated with the final visual acuity. CONCLUSIONS: The final visual prognosis was worse in patients with greater invasion of the central retinal zone, those with a longer interval between HSCT and the diagnosis of retinitis, and those who died. Prompt diagnosis of CMV retinitis through periodic fundus examinations of patients with CMV viremia can prevent severe vision loss. Once CMV viremia is confirmed, we recommend fundus examinations to be immediately performed and repeated every 2 weeks for at least 2 months, even if the CMV DNA titer in the peripheral blood becomes negative.

Electroretinography and retinal microvascular changes in type 2 diabetes.

PURPOSE: To assess whether functional (electrophysiological) parameters are related to changes in the structural (microvascular) parameters in diabetic retina. METHODS: This prospective cohort study included 380 eyes of patients with diabetes mellitus (DM) and 160 eyes of healthy controls. We analysed the electroretinogram (ERG) parameters and vascular parameters acquired from optical coherence tomography (OCT) angiography according to the diabetic retinopathy (DR) severity from early to late stages of DR. RESULTS: After exclusion, 366 eyes of diabetes and 157 eyes of controls were included in the analysis. The mean age at enrolment was 65.4 ± 7.8 years, and 177 (33.84%) were male. The amplitude and implicit time of the rod and cone and combined response ERG b-wave were significantly reduced and prolonged in the eyes of patients with DM, compared to the controls. There was a positive correlation between the amplitude and vessel density (VD) of the superficial plexus and a negative correlation between the implicit time and superficial VD in the scotopic and combined response b-wave. Interestingly, there was no correlation between electrophysiological parameters and deep VD. These correlations between electrophysiological parameters and vascular parameters were not significant in the non-diabetic, healthy control group. CONCLUSIONS: Functional and structural impairments precede the clinical manifestation of DR. We also found that these neural impairments, evaluated by ERG, were correlated with superficial VD. However, this correlation was absent in the healthy and early DR groups. These findings carefully suggest that neuronal dysfunction is linked to vascular dysfunction in type 2 diabetes.

Aqueous Humor Cytokine Levels in Diabetic Macular Edema Patients with Cotton-Wool Spots.

PURPOSE: To determine the characteristics of diabetic macular edema (DME) patients with cotton-wool spots (CWS). METHODS: We classified 80 treatment-naïve DME patients according to whether or not they had CWS involving macula and then compared the concentrations of interleukin- (IL-) 1ß, IL-6, IL-8, IL-10, IL-17, placental growth factor, vascular endothelial growth factor (VEGF), and intercellular adhesion molecule (ICAM)-1 in the aqueous humor between the groups, as well as optical coherence tomography (OCT) findings, baseline characteristics, and intravitreal bevacizumab responsiveness. RESULTS: Aqueous levels of ICAM-1 and VEGF in the group with CWS were significantly higher than those in the non-CWS (control) group (p < 0.001 and p = 0.006, respectively). In multiple logistic regression analysis to identify factors associated with CWS, the aqueous ICAM-1 (≥0.36 ng/mL) was significantly associated with CWS (odds ratio = 13.26, p < 0.001). Based on OCT, ellipsoid zone (EZ) disruption distribution was significantly different between the two groups (p = 0.038). Regarding responsiveness to treatment, although there was no significant difference in central subfield thickness between the two groups after treatments, the best-corrected visual acuity was worse in the group with CWS. CONCLUSIONS: The presence of CWS was accompanied by higher levels of aqueous ICAM-1. Based on OCT, EZ disruption was greater in DME patients with CWS, and their short-term visual prognosis was poorer.

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.

Tissue response of selective retina therapy by means of a feedback-controlled energy ramping mode.

BACKGROUND: The purpose of the study was to evaluate the safety and selectivity of the retinal pigment epithelium lesions by using automatic energy ramping and dosimetry technique for selective retina therapy and to investigate the healing response. METHODS: Ten eyes of Chinchilla Bastard rabbits were treated with an automatic dosage controlled selective retina therapy laser (frequency doubled Q-switched Nd:YLF, wavelength: 527 nm, pulse duration: 1.7 µs, repetition rate: 100 Hz, pulse energy: linear increasing from pulse to pulse up to shut down - maximal 110 µJ, max. number of pulses in a burst: 30, retinal spot diameter: 133 µm). After treatment, fundus photography, optical coherence tomography and fluorescein angiography were performed at three time points from 1 h to 3 weeks. Histological analysis was performed. RESULTS: A total of 381 selective retina therapy laser spots were tested (range 13-104 µJ).Typical fundus photographs obtained at 1 h after irradiation showed that 379 out of 381 lesions produced by selective retina therapy were not visible ophthalmoscopically and the lesions could be detected by angiography only. Optical coherence tomography images revealed that the structure of photoreceptors was preserved, but a disrupted retinal pigment epithelium layer was observed as was expected. By 3 weeks, histology showed selective retinal pigment epithelium damage without any effect on the inner retina and focal proliferation of the retinal pigment epithelium layer. CONCLUSIONS: Automatically controlled selective retina therapy is a significant improvement in this innovative treatment. It could be demonstrated that the non-contact, reflectometric technique with a controlled pulse energy ramp is safe and selective.