Performance of the AIDRScreening system in detecting diabetic retinopathy in the fundus photographs of Chinese patients: a prospective, multicenter, clinical study.

Background: Diabetic retinopathy (DR) is the leading cause of blindness in the working-age population worldwide, and there is a large unmet need for DR screening in China. This observational, prospective, multicenter, gold standard-controlled study sought to evaluate the effectiveness and safety of the AIDRScreening system (v. 1.0), which is an artificial intelligence (AI)-enabled system that detects DR in the Chinese population based on fundus photographs. Methods: Participants with diabetes mellitus (DM) were recruited. Fundus photographs (field 1 and field 2) of 1 eye in each participant were graded by the AIDRScreening system (v. 1.0) to detect referable DR (RDR). The results were compared to those of the masked manual grading (gold standard) system by the Zhongshan Image Reading Center. The primary outcomes were the sensitivity and specificity of the AIDRScreening system in detecting RDR. The other outcomes evaluated included the system's diagnostic accuracy, positive predictive value, negative predictive value, diagnostic accuracy gain rate, and average diagnostic time gain rate. Results: Among the 1,001 enrolled participants with DM, 962 (96.1%) were included in the final analyses. The participants had a median age of 60.61 years (range: 20.18-85.78 years), and 48.2% were men. The manual grading system detected RDR in 399 (41.48%) participants. The AIDRScreening system had a sensitivity of 86.72% (95% CI: 83.39-90.05%) and a specificity of 96.09% (95% CI: 94.14-97.54%) in the detection of RDR, and a false-positive rate of 3.91%. The diagnostic accuracy gain rate of the AIDRScreening system was 16.57% higher than that of the investigator, while the average diagnostic time gain rate was -37.32% lower. Conclusions: The automated AIDRScreening system can detect RDR with high accuracy, but cannot detect maculopathy. The implementation of the AIDRScreening system may increase the efficiency of DR screening.

Effect of Tauroursodeoxycholic Acid on Inflammation after Ocular Alkali Burn.

Inflammation is the main cause of corneal and retinal damage in an ocular alkali burn (OAB). The aim of this study was to investigate the effect of tauroursodeoxycholic acid (TUDCA) on ocular inflammation in a mouse model of an OAB. An OAB was induced in C57BL/6j mouse corneas by using 1 M NaOH. TUDCA (400 mg/kg) or PBS was injected intraperitoneally (IP) once a day for 3 days prior to establishing the OAB model. A single injection of Infliximab (6.25 mg/kg) was administered IP immediately after the OAB. The TUDCA suppressed the infiltration of the CD45-positive cells and decreased the mRNA and protein levels of the upregulated TNF-α and IL-1ß in the cornea and retina of the OAB. Furthermore, the TUDCA treatment inhibited the retinal glial activation after an OAB. The TUDCA treatment not only ameliorated CNV and promoted corneal re-epithelization but also attenuated the RGC apoptosis and preserved the retinal structure after the OAB. Finally, the TUDCA reduced the expression of the endoplasmic reticulum (ER) stress molecules, IRE1, GRP78 and CHOP, in the retinal tissues of the OAB mice. The present study demonstrated that the TUDCA inhibits ocular inflammation and protects the cornea and retina from injury in an OAB mouse model. These results provide a potential therapeutic intervention for the treatment of an OAB.

Th17 Activation and Th17/Treg Imbalance in Prolonged Anterior Intraocular Inflammation after Ocular Alkali Burn.

Ocular alkali burn (OAB) is a sight-threatening disease with refractory ocular inflammation causing various blinding complications. Th17 lymphocytes account for the pathogeneses of the autoimmune disease and chronic inflammation, but their role in prolonged anterior intraocular inflammation after OAB is still unknown. A rat OAB model was established for this purpose. Anterior intraocular inflammation was observed in both the acute and late phases of OAB, and histological examination confirmed the presence of inflammatory cell infiltration and fibrin exudation in the anterior segment. Luminex xMAP technology and qPCR were used to evaluate the intraocular levels of cytokines. The levels of IL-1ß, IL-6, and TNF-α were significantly elevated during the acute phase. The expression of IL-17A gradually increased from day 7 onwards and remained at a relatively high level. Immunofluorescence was performed to identify Th17 cells. CD4 and IL-17A double positive cells were detected in the anterior chamber from days 7 to 28. Flow cytometry showed that the frequency of Th17 cells increased in both lymph nodes and spleen, while the frequency of Treg cells remained unchanged, resulting in an elevated Th17/Treg ratio. The present study suggests that Th17 activation and Th17/Treg imbalance account for prolonged anterior intraocular inflammation after OAB.

Inhibition of endoplasmic reticulum stress by 4-phenylbutyrate alleviates retinal inflammation and the apoptosis of retinal ganglion cells after ocular alkali burn in mice.

OBJECTIVE: Retinal ganglion cell (RGC) apoptosis is one of the most severe complications that causes permanent visual impairment following ocular alkali burn (OAB). Currently, very few treatment options exist for this condition. This study was conducted to determine the effect of 4-phenylbutyric acid (4-PBA) on endoplasmic reticulum (ER) stress after OAB using a well-established OAB mouse model. METHODS: Ocular alkali burn was induced in C57BL/6 mouse corneas using 1 M NaOH. 4-PBA (10 mg/kg; 250 µL per injection) or saline (250 µL per injection) was injected intraperitoneally once per day for 3 days before the establishment of the OAB model. The apoptosis of retinal ganglion cells (RGCs) was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and the histological damage was examined by hematoxylin and eosin and immunofluorescence assay on retinal flat mounts. The key inflammatory response and the expression of ER stress-related markers in the retinal tissues were assessed by real-time PCR, western blotting and histologic analyses. RESULTS: 4-PBA significantly alleviated the apoptosis of RGCs and prevented the structural damage of the retina, as determined by the evaluation of RGC density and retinal thickness. Inhibition of ER stress by 4-PBA decreased the expression of vital proinflammatory cytokines, tumor necrosis factor alpha, and interleukin-1 beta; and suppressed the activation of retinal microglial cells and nuclear factor-kappa B (NF-κB). 4-PBA reduced the expression of the ER stress molecules, glucose-regulated protein 78, activated transcription factor 6, inositol-requiring enzyme-1 (IRE1), X-box-binding protein 1 splicing, and CCAAT/enhancer-binding protein homologous protein, in the retinal tissues and RGCs of OAB mice. CONCLUSIONS: The present study demonstrated that the inhibition of ER stress by 4-PBA alleviates the inflammatory response via the IRE1/NF-κB signaling pathway and protects the retina and RGCs from injury in an OAB mouse model. Such findings further suggest that 4-PBA might have potential therapeutic implications for OAB treatment.

METTL3 attenuates proliferative vitreoretinopathy and epithelial-mesenchymal transition of retinal pigment epithelial cells via wnt/ß-catenin pathway.

Proliferative vitreoretinopathy (PVR) is a refractory vitreoretinal fibrosis disease, and epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is the key pathological mechanism of PVR. However, few studies focused on the role of METTL3, the dominating methyltransferase for m6A RNA modification in PVR pathogenesis. Immunofluorescence staining and qRT-PCR were used to determine the expression of METTL3 in human tissues. Lentiviral transfection was used to stably overexpress and knockdown METTL3 in ARPE-19 cells. MTT assay was employed to study the effects of METTL3 on cell proliferation. The impact of METTL3 on the EMT of ARPE-19 cells was assessed by migratory assay, morphological observation and expression of EMT markers. Intravitreal injection of cells overexpressing METTL3 was used to assess the impact of METTL3 on the establishment of the PVR model. We found that METTL3 expression was less in human PVR membranes than in the normal RPE layers. In ARPE-19 cells, total m6A abundance and the METTL3 expression were down-regulated after EMT. Additionally, METTL3 overexpression inhibited cell proliferation through inducing cell cycle arrest at G0/G1 phase. Furthermore, METTL3 overexpression weakened the capacity of TGFß1 to trigger EMT by regulating wnt/ß -catenin pathway. Oppositely, knockdown of METTL3 facilitated proliferation and EMT of ARPE-19 cells. In vivo, intravitreal injection of METTL3-overexpressing cells delayed the development of PVR compared with injection of control cells. In summary, this study suggested that METTL3 is involved in the PVR process, and METTL3 overexpression inhibits the EMT of ARPE-19 cells in vitro and suppresses the PVR process in vivo.

Risk Factors and Prognosis of Pediatric Open Globe Injuries without Initial Light Perception.

PURPOSE: The aim of this study was to investigate the possible risk factors and prognosis of initial no light perception (NLP) in pediatric open globe injuries (POGI). PROCEDURES: This retrospective, comparative, interventional case-control study included 865 eyes of POGI patients presenting to a tertiary referral ophthalmic center from January 1, 2011 to December 31, 2015. Eyes were divided into 2 groups: the NLP group included eyes with initial NLP, and the light perception (LP) group included eyes with initial LP or vision better than LP. RESULTS: The following risk factors were significantly related to initial NLP: severe intraocular hemorrhage (OR 3.287, p = 0.015), retinal detachment (RD; OR 2.527, p = 0.007), choroidal damage (OR 2.680, p = 0.016), and endophthalmitis (OR 4.221, p < 0.001). Choroidal damage is related to remaining NLP after vitreoretinal surgery (OR 12.384, p = 0.003). At the last visit, more eyes in the NLP group suffered from silicone oil-sustained status (OR 0.266, p = 0.020) or ocular atrophy (OR 0.640, p = 0.004), and fewer eyes benefitted from final LP (OR 41.061, p < 0.001) and anatomic success (OR 4.515, p < 0.001). CONCLUSION: Severe intraocular hemorrhage, RD, choroidal damage, and endophthalmitis were possible predictors of initial NLP in POGI. Choroidal damage was the major factor related to an NLP prognosis. Traumatized eyes with initial NLP could be anatomically and functionally preserved by vitreoretinal surgery.

Transforming ophthalmic education into virtual learning during COVID-19 pandemic: a global perspective.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has imposed measures of social distancing and barriers in delivery of "in person" education. Institutions, involved in training the next generation of ophthalmologists, are using alternative teaching methods to maintain the standard of education. METHODS: We conducted a worldwide survey among physicians, who are actively involved in Ophthalmology-related education, between 3 and 14 April 2020. The expert survey, developed on the basis of literature search and focus group discussions, comprised 23 questions addressing the use of e-learning in Ophthalmology during the COVID-19 pandemic. RESULTS: A total of 321 participants from both academic and non-academic institutions worldwide, with variable practice experience and expertise, completed the survey. Before the pandemic, the majority of participants used traditional training modalities, including lectures, grand rounds and journal clubs, and 48% did not use any e-learning. There was a statistically significant increase in the use of all e-learning alternatives during the pandemic (p < 0.001), associated mainly with the availability of e-learning facilities (p < 0.001) and the academic character of institutions (p < 0.001). Zoom® was recognized as the mostly used platform for virtual teaching. Although theoretical teaching may take place, the surgical training of residents/fellows was dramatically reduced. The latter was significantly associated with participants' perspectives about teaching practices (p < 0.001). CONCLUSION: COVID-19 pandemic imposed great challenges in the educational field of Ophthalmology. The experience related to virtual training in Ophthalmology, gained during the pandemic, may change the traditional teaching practices in the world and provide new educational opportunities.

Risk Factors Associated with Failure of Direct Cyclopexy in the Treatment of Small to Moderate Tramatic Cyclodialysis Clefts.

BACKGROUND: To evaluate the risk factors associated with failure to correct hypotony using direct cyclopexy in patients with traumatic cyclodialysis cleft. METHODS: In a series of 116 patients with traumatic cyclodialysis who underwent direct cyclopexy at Zhongshan Ophthalmic Center from January 2008 to August 2018, the clinical correlation between the risk factors and failure of the operation were retrospectively studied, after adjusting for other potential confounders. RESULTS: The curative ratio after one procedure was 82.76%, whereas 20 (17.24%) eyes experienced treatment failure after the first surgery. The degree of anterior chamber angle closure was significantly wider in patients with a failed first surgery than in patients for whom one procedure was a success (p = .046). The risk of failure to achieve closure increased as the angle-closure exceeded 5 clock hour (odds ratio, 10.39; 95% confidence interval, 1.75-61.72; p = .010). An analysis of the recurrent position indicated that an angle closure exceeding 5 clock hour may impede accurate cleft location and is thus associated with an increased risk of failure to correct hypotony. CONCLUSION: Exceeding the threshold of 5 clock hour in anterior chamber angle closure may impede accurate cleft location and, thus, present a higher risk of failure to correct hypotony using direct cyclopexy. These patients may need injection of a viscoelastic agent into the anterior chamber by paracentesis to deepen the anterior chamber and to delineate the clefts using gonioscopy pre- or intraoperatively.

Risk Factors for Trauma-Related Eviscerations: Analysis of 821 Cases.

Evisceration is the end therapeutic approach for the treatment of severe ocular trauma cases, and it is a tremendous loss for patients. In this study, we explored the changing trends in the number of surgeries performed, demographic data and ocular features, and risks for early evisceration, aiming to provide more data for the additional prevention and management strategies for this catastrophic problem. This was a retrospective study that included patients who underwent ocular evisceration at the Zhongshan Ophthalmic Center between January 2013 and December 2017. A total of 1229 evisceration cases were reviewed, and only trauma-related eviscerations were analyzed. Etiology, demographic data, ocular features, and hospitalization time were evaluated. The total number of trauma-related eviscerations recorded in the past five years was 821 cases. The number of surgeries performed was almost constant each year (164 ± 17 cases); 35% of the patients were less than ten years old at the time of the original ocular injury and 69% of them were male. Endophthalmitis led to significantly early evisceration compared with cases without endophthalmitis (P < 0.05). The group with a history of silicone oil tamponade showed a significantly longer surgical interval between trauma and evisceration than did the nonsilicone oil tamponade group (P < 0.05). Day-case hospitalization for evisceration increased from 0% to 32% over the past five years. The results of the present study show that the number of ocular trauma-related eviscerations performed in the past five years was almost unchanged and boys under ten are highly susceptible. This study also demonstrates that endophthalmitis leads to significantly early evisceration, and silicone oil tamponade may postpone ocular atrophy. Based on the study data, day-case surgery is safe for evisceration management.

Effect of vitrectomy with intrasurgical regulation of intraocular pressure in a rabbit model of central retinal artery occlusion.

Central retinal artery occlusion (CRAO) is an ophthalmic emergency that causes severe and permanent visual impairment. The effects of conventional treatments on recanalizing retinal arteries and improving visual outcome are equivocal. This study was designed to determine the possible benefits of pars plana vitrectomy (PPV) with intrasurgical regulation of intraocular pressure using intraocular vascular counterpulsation (IVT). CRAO was induced by 532-nm argon green laser activation of auricular intravenous injected rose bengal, a photosensitive dye, in the central retinal arteries (CRA) of eighty-four New Zealand white albino rabbits. CRAO rabbits were randomly assigned to photocoagulation, vitrectomy and counterpulsation groups. Depending on the time intervals between surgery and CRAO induction, vitrectomy and counterpulsation groups were further divided into 2 h (2h), 6 h (6h) and 24 h (24h) subgroups. The proportion of eyes with complete recanalization was significantly higher in the 2h counterpulsation subgroup after three days (P = 0.032) and in all counterpulsation subgroups after one week (P = 0.020). After one month, the 2h and 6h counterpulsation subgroups showed greater oscillatory potential (OPs) responses (F = 3.519, P = 0.049). The 2h counterpulsation subgroup also exhibited greater b-wave amplitude in photopic 3.0 Flicker(F = 4.530, P = 0.044). Histologic evaluation revealed less destruction in the inner retina for the 2h and 6h counterpulsation subgroups. Expression of HSP70 was higher in the 2h and 6h counterpulsation subgroups (F = 48.915,P < 0.001). Levels of HSP90 were lower in all counterpulsation subgroups (F = 30.065,P < 0.001). Levels of TNF-α were lower in the 2h counterpulsation subgroup (F = 14.762,P < 0.001). These results indicate that PPV with IVT was effective to recanalize retinal arteries after CRAO. Early intervention provided better morphologic and functional prognosis for inner retina. The protective effect was related with higher retinal levels of HSP70 and lower levels of HSP90 and TNF-α.

Landscape of microRNA in the aqueous humour of proliferative diabetic retinopathy as assessed by next-generation sequencing.

BACKGROUND: The microRNAs (miRNA) have been found to play an important role in the pathogenesis of diabetic retinopathy. We try to explore the miRNA and piwi-interacting RNA (piRNA) profile in the aqueous humour of proliferative diabetic retinopathy (PDR) using next-generation sequencing (NGS). METHODS: Aqueous humour samples were collected from nine PDR eyes and nine cataract control eyes, and NGS was performed. Quantitative polymerase chain reaction (qPCR) was used to validate the sequencing results. An oxygen-induced retinopathy (OIR) model was used to validate the angiogenesis related miRNA. RESULTS: In total, 484 miRNAs were differently expressed between the PDR eyes and cataract control eyes, including 210 mature miRNAs and 274 novel miRNAs. Furthermore, eight miRNAs and 30 piRNAs were identified as the most differently expressed between the two groups (P > .85). This differential expression of miRNA was predicted to regulate Rho protein signal transduction, neurotransmitter uptake and histone lysine methylation. Relative expression patterns of miR-184, -150-5p and -93-5p were confirmed by qPCR. A reduced expression of miR-93-5p was confirmed in the OIR model. CONCLUSIONS: This study comprehensively demonstrated the miRNA and piRNA expression profile of the aqueous humour of PDR eyes, which may serve as a potential biomarker and involved in the pathogenesis of PDR.

Mutation Spectrum of the LRP5, NDP, and TSPAN12 Genes in Chinese Patients With Familial Exudative Vitreoretinopathy.

Purpose: LRP5, NDP, and TSPAN12 are known to be associated with familial exudative vitreoretinopathy (FEVR). In this study, a comprehensive mutation screening for the three genes was performed in patients with a clinical diagnosis of FEVR in Han Chinese. Methods: Genomic DNA and clinical data were collected from 100 probands and their family members. Sanger sequencing was performed to screen for LRP5, NDP, and TSPAN12 mutations and phenotype-genotype correlation was analyzed. Results: There were 23 causative mutations identified in 23 unrelated probands (10/23 in LRP5, 8/23 in TSPAN12, and 5/23 in NDP). Apart from NDP mutations, only two LRP5 mutations inherited in an autosomal recessive manner. Among the 23 causative mutations, 13 were novel variants (4/10 in LRP5, 6/8 in TSPAN12, and 3/5 in NDP). According to the modified classification system, statistical significance was observed in the distribution of mutated genes (P = 0.049). None of the causative mutations was found in group I FEVR. Probands with LRP5 or NDP mutations were mainly categorized into group III and IV, TSPAN12 mutations were mainly observed in probands with group IV and V FEVR. Conclusions: The detection rate for mutations in the three known genes was 23%. Mutations in LRP5 and TSPAN12 were more frequent, accounting for 10% and 8%, respectively. The NDP mutations were only identified in 6% in this cohort. There were 13 novel variants found, which provided a deeper understanding of this disease. Potential phenotype-genotype correlation was observed in the modified system. TSPAN12 mutations might lead to the most severe phenotype.

CLINICAL FEATURES OF AFFECTED AND UNDETACHED FELLOW EYES IN PATIENTS WITH FEVR-ASSOCIATED RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To report the clinical characteristics of the affected and fellow eyes in patients with familial exudative vitreoretinopathy-associated rhegmatogenous retinal detachment (FEVR-RRD). METHODS: This was a retrospective observational case series. The affected and fellow eyes were given complete examinations. The age, sex, clinical features of the affected eyes, and varied abnormalities of the fellow eyes were analyzed. RESULTS: Forty-three patients with FEVR-RRD were included. The average age was 21.8 ± 10.9 years, and the males (19.9 ± 9.6) were younger than the females (28.1 ± 1.2). Retinal round holes were noted in 32 (71.1%) eyes. In addition, horseshoe retinal tears and giant retinal tears were present in 10 (22.2%) eyes and 3 (6.7%) eyes. Subretinal fibrosis was seen in 20 (44.4%) eyes, and choroidal detachment was shown in 6 (13.3%) of the eyes. A high prevalence of abnormalities was noted in the undetached fellow eyes in the peripheral retina, including vascular leakage in fundus fluorescein angiography (75.6%), lattice degeneration (53.7%), and vitreous traction (51.2%). CONCLUSION: Male patients with FEVR-RRD experience an earlier onset than females in our series. Retinal tears, even giant tears, could be responsible for FEVR-RRD. The fellow eyes of FEVR-RRD patients were characterized by predetachment changes, which need both lifelong monitoring and timely vision-saving intervention.

Novel mutations in FZD4 and phenotype-genotype correlation in Chinese patients with familial exudative vitreoretinopathy.

PURPOSE: To identify novel mutations in the frizzled 4 (FZD4) gene in patients with familial exudative vitreoretinopathy (FEVR) in southern China and to delineate the mutation-associated clinical manifestations. METHODS: Clinical data and genomic DNA were collected from 100 probands and their family members. The coding regions of FZD4 were screened for mutations with PCR and Sanger sequencing. Cosegregation analysis was used to verify suspected variants, and clinical symptoms in the probands were analyzed. RESULTS: Fourteen causative heterozygous mutations in FZD4 in 21 unrelated probands were noted, in 21.0% of the index patients (21/100). Four novel missense mutations (C45R, C45S, C53S, and C90R) and three novel deletion mutations (T326fsX356, G492fsX512, and S345_A351del) with a high possibility of pathogenicity were detected. None of these mutations were found in current online databases and 150 ethnically matched control subjects without retinopathy. The majority of the mutations in FZD4 were identified in probands with retinal folds (15/21) and ectopic macula (5/21). No mutations in FZD4 were found in probands with complete tractional retinal detachment in infancy or with mild asymptomatic FEVR in adulthood. CONCLUSIONS: Seven novel mutations found in this study have broadened the spectrum of mutations in FZD4 known to cause FEVR, providing a deeper understanding of this disease. The results show that mutations in FZD4 are associated with the phenotypes of retinal folds or ectopic macula in FEVR but might not be associated with extreme severe bilateral FEVR during infancy, at least in southern Chinese patients.

Macrophage polarization in experimental and clinical choroidal neovascularization.

Macrophages play an important role in the development of age-related macular degeneration (AMD). In this study, the spatial and temporal changes and the polarization of macrophages in murine laser-induced choroidal neovascularization (CNV) were investigated, and the polarized M1 and M2 biomarkers in the aqueous humors of neovascular AMD (nAMD) patients were studied. Macrophages, the main infiltrating inflammatory cells in CNV lesions, were evidenced by a significant increase in F4/80 mRNA expression and by the infiltration of F4/80+ cells in the lesions and the vicinity of laser-induced CNV. The mRNA expressions of M1-related markers were dramatically upregulated in the early stage, while the M2-related markers were slightly upregulated in the middle stage and sustained until the late stage. The results of immunostaining showed a similar early-but-transient M1 pattern and a delayed-but-sustained M2 pattern in laser-induced CNV. In addition, a higher M2/M1 ratio was found in both the murine models (Arg-1/iNOS and CCL22/CXCL10) and the aqueous humors of nAMD patients (CCL22/CXCL10) than in the controls. Our results suggested that the dynamic patterns of M1 and M2 were different in both the experimental and clinical CNV. The M2 macrophages were predominant and may play a more important role in the development of CNV.

Aqueous humor cytokine profiling in patients with wet AMD.

PURPOSE: To investigate the chemokine expression profiles in the aqueous humor of wet age-related macular degeneration (wet AMD) patients and to correlate their levels with clinical findings. METHODS: Undiluted aqueous humor samples (100-200 µl) were obtained from 16 wet AMD eyes and 12 control eyes. Forty chemokines were measured using a multiplex method. A 6×6 mm area of the macular region centered on the fovea was examined using spectral domain optical coherence tomography (SD-OCT). RESULTS: The detection rates were 50% or more for 15 chemokines. Compared with the control group, the aqueous humor in wet AMD patients showed a significantly higher expression of CXCL10 (p=0.004), CCL14 (p=0.002), CXCL16 (p=0.013), CXCL7 (p=0.033), and CCL22 (p=0.037), while growth-related oncogene (GRO) was significantly decreased in the wet AMD patients (p=0.001). When compared with treatment-naïve patients, the recurrent group had significant upregulation of CXCL10 (p=0.012) and CCL22 (p=0.002). CXCL16 was positively correlated with lesion size, and CCL22 was higher in patients whose OCT images showed intraretinal fluid (IRF) or hyperreflective foci (HF). CONCLUSIONS: Elevated levels of inflammation-related chemokines, including CXCL10, CCL14, CXCL16, CXCL7, and CCL22, in the aqueous humor of AMD patients may suggest a pathogenic role for inflammation. CXCL10 and CCL22 were more elevated in eyes with recurrent wet AMD than in treatment-naïve eyes. CXCL16 was positively correlated with lesion size. The increase in CCL22 was correlated with the presence of IRF or HF. These data may be of interest in the search for biomarkers associated with wet AMD and may potentially indicate different treatment strategies.

INCREASED POSTERIOR RETINAL VESSELS IN MILD ASYMPTOMATIC FAMILIAL EXUDATIVE VITREORETINOPATHY EYES.

PURPOSE: To document a new clinical manifestation in familial exudative vitreoretinopathy (FEVR) eyes, especially in mild asymptomatic eyes with normal vision. METHODS: Twenty individuals with mild Stage I or II FEVR with a conventional "normal-appearing" posterior pole and 20 healthy control eyes were recruited. The crossing numbers of retinal vessels with peripapillary inner reference circle, peripapillary outer reference circle, peripapillary temporal inner arc, peripapillary temporal outer arc, and branching points between the peripapillary outer reference circle and peripapillary inner reference circle were counted. Vessel bifurcation was evaluated by B/CI (defined as the branching number divided by the crossing number on peripapillary inner reference circle) and CO/B (crossing number on peripapillary outer reference circle divided by the branching number) ratios. The inter- and intraobservers' agreements were analyzed. All these parameters were compared between FEVR and control groups. RESULTS: The coefficient of repeatability for the parameters ranged from 2.597 to 5.096, and the intraclass correlation coefficients were all above 0.85. All the parameters showed good interobserver agreement with a narrow range of 95% limit of agreement (from -3.16 to 3.37) and high Pearson correlation (P < 0.001). The mean crossing numbers on peripapillary inner reference circle, peripapillary outer reference circle, peripapillary temporal inner arc, peripapillary temporal outer arc, and the branching numbers were larger in the FEVR group. No significant differences were found in CO/B and B/CI ratios. CONCLUSION: Patients with FEVR have more vessels radiated from the optic disk in the posterior pole. Unlike the increased vessels in the peripheral retina, the increasing pattern of peripapillary vascularity in patients with FEVR does not appear to have a component of overbifurcation. This is a new documented clinical manifestation in patients with FEVR. Attention to an increased or arrangement pattern of retinal vessels may aid in the screening of FEVR.

Posterior pole retinal abnormalities in mild asymptomatic FEVR.

PURPOSE: To describe the posterior retinal abnormalities in asymptomatic mild familial exudative vitreoretinopathy (FEVR) individuals who are normal in conventional clinical examination. METHODS: Thirty-eight asymptomatic mild FEVR individuals (38 eyes) and 38 controls (38 eyes) were included in this cross-sectional study. The posterior retinas in each individual appeared normal. The diagnosis of FEVR was made based on a positive FEVR family history and the presence of retinal peripheral avascular zone with other vessel abnormalities. Biometric data from fundus photographs and fluorescein fundus angiography of all subjects were studied. The diameter of the optic disc (DD), the disc-to-macula distance (DM), the ratio of DM/DD, and numbers of retinal vessels radiated from the optic disc were measured. RESULTS: Significant anatomic differences were identified in the eyes of patients with asymptomatic FEVR compared with those of the control subjects. In individuals with stage I or II FEVR, DD was smaller (1605.34 ± 250.60 vs. 1733.39 ± 163.79 µm), DM was larger (5434.08 ± 824.82 vs. 4696.29 ± 257.34 µm), and DM/DD was higher (3.49 ± 0.93 vs. 2.73 ± 0.28) than those of the controls. Peripapillary retinal vessels were increased significantly in FEVR compared with the controls (24.53 ± 3.10 vs. 21.39 ± 2.65). CONCLUSIONS: Asymptomatic individuals with stage I or II FEVR had several abnormalities in the posterior pole noted with more retinal vessels, a significantly larger disc-to-macula distance as well as a remarkably smaller optic disc with a decreased horizontal diameter. These findings will facilitate the early diagnosis of FEVR and are important for adequate genetic counseling as well as the prevention and treatment of this disease.

Ultrasonographic feature of persistent hyperplastic primary vitreous.

PURPOSE: To observe the ultrasonographic features of patients with persistent hyperplastic primary vitreous (PHPV). METHODS: Thirty-two subjects (34 eyes) diagnosed with PHPV were evaluated by ultrasonography. RESULTS: The ultrasonography demonstrated a retrolental mass extending from the optic disc to the posterior lens capsule, manifested as band, regular triangle, or inverted triangle shapes. The band-shaped echo was characterized as a linear band extended from the optic disc to the posterior lens capsule. The regular triangle-shaped echo was manifested as a membranous septum with a wide base extended from the optic disc to the posterior lens capsule, and the anterior part became narrower. The inverted triangle echo was characterized as a membranous septum with a narrow base extended from the optic disc to the posterior lens capsule, and the anterior part become wider. CONCLUSION: Ultrasonography is noninvasive and safe, and can offer real-time display of intraocular structures. This is especially important in individuals who are uncooperative or unsuitable for fundus examination due to media opacity. Combined with clinical feature, ultrasonography provides vital evidence for the diagnosis of PHPV. Thought observing ultrasonographic feature, clinicians could evaluate the size, position and severity of lesions in PHPV patients, and which would be helpful to determine the surgical approach and clinical prognosis.

[Comparison of different power-density krypton laser combined with Nd:YAG laser peripheral iridotomy].

PURPOSE: To compare the influence of krypton laser with different power densities combined with Nd:YAG laser peripheral iridotomy (LPI) on the intraocular pressure, blood-aqueous barrier and inflammatory of anterior chamber as well as the therapeutic effect. METHODS: Using a laser flare cell meter and Goldmann tonometer, the level of aqueous protein, the number of cells in the anterior chamber and intraocular pressure of 31 patients (62 eyes) who underwent krypton laser with different power densities combined with Nd:YAG laser peripheral iridotomy were examined and recorded preoperatively and postoperatively. RESULTS: The mean preoperative and 1-hour, 3-day, 7-day, 1-month postoperative intraocular pressure (IOP) of the high power-density group were (15.68 +/- 2.41), (27.13 +/- 3.48), (20.97 +/- 5.27), (16.35 +/- 1.14) and (15.06 +/- 2.02) mmHg, while those of the low were (15.35 +/- 1.78), (22.77 +/- 3.26), (16.26 +/- 2.41), (15.68 +/- 2.06) and (15.06 +/- 1.36) mmHg. The mean preoperative and 3-day, 7-day, 1-month postoperative flare intensity of the high power-density group were (4.65 +/- 1.50), (10.41 +/- 2.47), (7.31 +/- 2.31) and (6.15 +/- 2.16) pc/ms, while those of the low were (4.45 +/- 1.19), (6.47 +/- 1.11), (4.81 +/- 0.55) and (4.98 +/- 1.48) pc/ms. The number of aqueous cells of the high was (0.47 +/- 0.42), (36.22 +/- 9.16), (18.54 +/- 3.60) and (6.29 +/- 0.98), while that of the low was (0.58 +/- 0.52), (24.73 +/- 6.09), (10.61 +/- 1.70) and (2.96 +/- 1.35). The mean 1-hour and 3-day postoperative IOP of the high was higher than that of the low. Both the mean flare intensity and the mean number of aqueous cells of the high power-density group were higher than those of the low. The differences were of statistical significance (P < 0.05). The mean flare intensity of the high power-density group in the 1-month postoperative follow-up was still higher than the baseline. The mean number of aqueous cells of both the high and the low power-density groups in the 1-month postoperative follow-up was still higher than the baseline. During 1-month follow-up, no obvious visual damage, diffuse corneal endothelial burns or corneal decompensation, lens injury and closure of the peripheral iris incision were observed. CONCLUSION: When krypton laser combined with Nd:YAG laser peripheral iridotomy is under consideration, relatively low power-density krypton laser is recommended because it can achieve the similar therapeutic effects as high power-density krypton laser but leads to less complications and a briefer recovery. More follow-ups are needed after LPI, because the number of aqueous cells in 1-month follow-up was still abnormal.