Observation of retinal neovascularization using optical coherence tomography angiography after panretinal photocoagulation for proliferative diabetic retinopathy.

BACKGROUND: To describe the longitudinal changes in retinal neovascularization elsewhere (NVE) as observed on optical coherence tomography angiography (OCTA) in proliferative diabetic retinopathy (PDR) treated by panretinal photocoagulation (PRP). METHODS: Each patient included in this prospective clinical study was newly diagnosed with PDR and NVE confirmed by both fundus fluorescein angiography (FFA) and OCTA. They received four sessions of PRP using a multiwavelength laser. Best-corrected visual acuity (BCVA) and OCTA images of the NVE were obtained before each PRP session and at 1 month, 3 months, and 6 months after the PRP treatment. Generalized estimating equations (GEE) was used to investigate the differences between the BCVA and NVE areas before and after PRP. RESULTS: Thirty-two eyes of 32 patients with a mean age of 50.56 ± 7.05 years were included. We found a statistically significant reduction in the NVE area at all time points compared with the baseline except at 6 months (all P < 0.05). Further analysis demonstrated no statistically significant change in the NVE area between two adjacent timepoints except from baseline to post-1st PRP (P < 0.05). BCVA at 3 months showed a statistically significant improvement compared with baseline (P < 0.05), but no significant changes in BCVA were observed during the other visits. CONCLUSIONS: We found an overall regression in the NVE area following PRP starting as early as 1 week after the 1st session and lasting up to 3 months. OCTA provides quantitative information on vascular changes and could be a practical method for the longitudinal evaluation of neovascularization.

PHENOTYPIC VARIABILITY OF RECESSIVE RDH12-ASSOCIATED RETINAL DYSTROPHY.

PURPOSE: To characterize the phenotypic variability and report the genetic defects in a cohort of Chinese patients with biallelic variants of the retinol dehydrogenase 12 (RDH12) gene. METHODS: The study included 38 patients from 38 unrelated families with biallelic pathogenic RDH12 variants. Systematic next-generation sequencing data analysis, Sanger sequencing validation, and segregation analysis were used to identify the pathogenic mutations. Detailed ophthalmic examinations, including electroretinogram, fundus photography, fundus autofluorescence and optical coherence tomography, and statistical analysis were performed to evaluate phenotype variability. RESULTS: Twenty-five different mutations of RDH12 were identified in the 38 families. Six of these variants were novel. Val146Asp was observed at the highest frequency (23.7%), and it was followed by Arg62Ter (14.5%) and Thr49Met (9.2%). Twenty-three probands were diagnosed with early-onset severe retinal dystrophy, 6 with Leber congenital amaurosis, 7 with autosomal recessive retinitis pigmentosa, and 2 with cone-rod dystrophy. Self-reported nyctalopia occurred in about a half of patients (55.3%) and was significantly more common among older patients (P < 0.01). Nyctalopia was not significantly associated with best-corrected visual acuity (P = 0.72), but older patients had significantly greater best-corrected visual acuity loss (P < 0.01). Only 15.8% of the patients had nystagmus, which was significantly more likely to occur among 36.8% of the patients with hyperopia >3D (P < 0.01) and/or in cases of reduced best-corrected visual acuity (P = 0.01), but was not associated with age (P = 0.87). CONCLUSION: Several high-frequency RDH12 variants were identified in patients with inherited retinal dystrophies, most of which were missense mutations. Variable but characteristic phenotypes of a progressive nature was observed. Overall, the findings indicated that biallelic RDH12 mutations are a common cause of early-onset retinal dystrophy and a rare cause of cone-rod dystrophy.

Sphere-Induced Rejuvenation of Swine and Human Müller Glia Is Primarily Caused by Telomere Elongation.

Müller cells are the major supportive and protective glial cells in the retina with important functions in histogenesis and synaptogenesis during development, and in maintenance of mature neurons as they show to secrete various cytokines and manifest potentials of self-renewal and transdifferentiation into retinal neurons following injury in the vertebrate retinas. The swine retina has a visual streak structure similar to the human macular where cone photoreceptors are highly concentrated, thereby can serve as a better model for studying retinal diseases and for formulating cell-based therapeutics than the rodent retinas. Like most differentiated somatic mammalian cells, the isolated swine and human Müller glia become senescent over passages in culture, which restricts their potential application in basic and clinic researches. Here, we demonstrate that the senescence of swine and human Müller cells is caused by telomere attrition upon multiplications in vitro; and the senescent cells can be rejuvenated by sphere suspension culture. We also provide evidence that sphere-induced extension of telomeres in swine and human Müller glia is achieved by alternative lengthening of telomeres or/and by telomerase activation. Stem Cells 2017;35:1579-1591.

Longitudinal observation of subretinal fibrosis in Vogt-Koyanagi-Harada disease.

BACKGROUND: Subretinal fibrosis (SRF) is a vision-threatening complication of Vogt-Koyanagi-Harada disease (VKH). It has long been recognized as a sequela of chronic inflammation. The developmental process of SRF, however, has not been described. The purpose of this study is to provide longitudinal observations of SRF in VKH. METHODS: Retrospective chart review of 10 VKH patients referred to our group between January 2008 and September 2015 at acute uveitic stage with SRF at presentation or who developed SRF during follow up. RESULTS: Ten patients (6 males and 4 females) with a median age of 39.0 (range, 23 to 58) years old were included. The median disease duration at presentation and median duration of follow up were 25.5 (range 5 to 60) days and 32.5 (range 13 to 61) months respectively. At presentation, all patients except one had been inappropriately treated with glucocorticosteroid (insufficiently dosed or tapered too fast) for longer than 2 weeks. Despite large dose oral glucocorticosteroid (1 mg/kg/d prednisone or equivalent) with slow tapering in combination with at least one immunomodulatory agent (cyclosporin A, cyclophosphamide or azathioprine) after presentation, all patients developed bilateral SRF within the first 4 months of disease course and 7 patients within the first 2 months. In 8 patients, shape-change/migration and progressive proliferation/pigmentation of SRF was observed over a period of several months after its formation, and then became quiescent but may further underwent depigmentation or pigmentation. SRF involved macula in 12 eyes (7 patients) and caused treatment resistant macular detachment and severe visual impairment in 6 eyes (4 patients). At the last visit, eyes with macular involvement were more common to had worse final best corrected visual acuity (≤20/50) than those without (9/12 vs. 0/8, p = 0.001). CONCLUSIONS: SRF usually develop early in the disease course in VKH patients who are not adequately controlled; it usually undergoes a highly dynamic process within the subretinal space and may involve the macula and resulted in poor final visual outcome.

Internal limiting membrane transplantation for unclosed and large macular holes.

BACKGROUND: To present the surgical technique and clinical outcomes of transplantation of autologous internal limiting membrane (ILM) for large macular holes (MHs) after failed surgeries with ILM removal. METHODS: Thirteen eyes of 13 consecutive patients with MHs larger than 500 µm after failed surgeries with ILM removal underwent vitrectomy with transplantation of autologous ILM. In the ILM transplantation technique, a small piece of the ILM was peeled off and transplanted inside the macular hole. Fluid-air exchange was then performed. The air was then replaced with 10 % perfluoropropane (C3F8) gas. Comprehensive ophthalmologic examinations and spectral-domain optical coherence tomography were performed preoperatively and postoperatively. The main outcome measures were best-corrected Snellen visual acuity (BCVA) and MH closure rate. RESULTS: The preoperative mean base diameter of the MHs was 1637.6 + 412.7 µm (range, 814-2092 µm). The preoperative mean minimum diameter was 814.4 + 255.0 µm (range, 546 µm-1485 µm). Complete MH sealing was achieved in 12 eyes after transplantation of the ILM flap. The mean BCVA was 1.15 + 0.21 (range, 1.0-1.6) before surgery and 0.99 + 0.17 (range, 0.7-1.3) at 12 months postoperatively. There was a significant difference in BCVA before versus after the surgery (t = 3.825, P = 0.0002, paired t- test). CONCLUSIONS: Transplantation of autologous ILM is an effective addition to the surgical options for large macular holes after failed surgeries with ILM removal.

[Clinical study of vitrectomy with epiretinal membrane peeling for idiopathic macular epiretinal membrane].

OBJECTIVE: To investigate the result of vitrectomy with epiretinal membrane (ERM) peeling for idiopathic macular epiretinal membrane (IMEM). METHODS: Clinical data of 51 patients (51 eyes) of IMEM who underwent vitrectomy with ERM peeling were retrospectively investigated. All the patients were examined by visual acuity, slit lamp, fundus under mydriasis, optical coherence tomography (OCT) before and after the surgery. The 3-18 months follow-up were included, mean (5.8±3.2) months. All the macular ERM were removed successfully. Paired-sample t test was used to study the visual acuity and macular foveal thickness before and after surgery. The Pearson correlation analysis was used to study the correlation between visual acuity and macular foveal thickness. RESULTS: In the 51 patients, the best visual acuity improved from 4.25±0.34 to 4.65±0.23 postoperatively. The difference was statistically significant (t=-9.012, P=0.000), and the mean foveomacular thickness decreased from (432.7 ± 91.7) to (333.3 ± 66.1)µm postoperatively, the difference was statistically significant (t=10.565, P=0.000). There was negative correlation between visual acuity and mean foveomacular thickness (r=- 0.452, P=0.001), and it was obvious postoperatively (r=-0.602, P=0.000). The increase of visual acuity was strongly correlated with the decline of mean foveomacular thickness (r=0.382, P=0.006). Twelve eyes have developed cataract in 3 to 6 months after vitrectomy which affect the visual acuity. All of them went phacoemulsification and intraocular lenses(IOL) implantation and visual acuity after surgery had an obviously improvement. CONCLUSIONS: Vitrectomy with ERM peeling can improve visual acuity and ease macular edema. And it is a safe and effective therapy to treat patients of IMEM.

Systemic lupus erythematosus and antiphospholipid syndrome related retinal vasculitis mimicking ocular cysticercosis: a case report.

Making accurate and timely diagnosis is often challenging when patients with a systemic disease first present with ocular manifestations. The possibility that vasculitis associated with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) can be misdiagnosed as cysticercosis has not been discussed in the literatures.

Novel ALMS1 mutations in Chinese patients with Alström syndrome.

PURPOSE: Alström syndrome (AS) is a rare monogenic autosomal recessively inherited disorder characterized by cone rod dystrophy and multiple organ dysfunction. Mutations in the Alström syndrome 1 (ALMS1) gene have been found to be causative for AS. The purpose of this study was to identify ALMS1 mutations and to assess the clinical features of Chinese patients with AS. METHODS: Detailed ocular and laboratory examinations were performed. Peripheral blood samples were collected from patients and their parents. Genomic DNA was extracted with a Qiagen kit. Exons and exon/intron junctions of ALMS1 were amplified with polymerase chain reaction (PCR) and screened for mutations with Sanger sequencing. The results were compared with the ALMS1 transcript to exclude polymorphisms and confirm pathogenic mutations. RESULTS: Seven patients from five unrelated non-consanguineous families were diagnosed with AS. All patients had cone rod dystrophy with impaired visual acuity, photophobia, and nystagmus. Other clinical features, including sensorineural hearing loss, truncal obesity, insulin resistance, type 2 diabetes mellitus, renal and hepatic dysfunction, hyperlipidemia, hypothyroidism, mental retardation, acanthosis nigricans, and scoliosis, were present. Sequencing revealed two novel mutations, p.N3150Kfs2X and p.V3154Xfs, in patient 1; one novel mutation, p.N3672Ifs11X, and one previously reported nonsense mutation, p.R3703X, in patient 2; novel mutations p.S2479X and p.R3611Efs7X in patient 3; one novel homozygous mutation, p.S695X, in patients 4 and 5; and two novel mutations, p.H688HfsX and p.Q3147Qfs2X, in patients 6 and 7. These mutations were not present in 100 unrelated healthy Chinese control subjects. The patients' parents were heterozygous carriers of the mutant allele. CONCLUSIONS: Seven Chinese patients with AS showed typical ophthalmic features and multiple organ dysfunction. Novel loss of function mutations in the ALMS1 gene are the underlying genetic defects.

Transthyretin Ala36Pro mutation in a Chinese pedigree of familial transthyretin amyloidosis with elevated vitreous and serum vascular endothelial growth factor.

The familial transthyretin (TTR) amyloidosis (FTA) demonstrates variable penetrance of clinical features associated with mutations in the plasma thyroid hormone-binding protein TTR gene. The purpose of this study was to assess the ocular features, to analyze vitreous and serum vascular endothelial growth factor (VEGF) levels, and to identify the genetic defect in a Chinese family with TTR FTA. The pedigree of interest was a three-generation family with eleven members. The primary ocular signs were vitreous opacities, beginning from the third or fourth decade, accompanied by retinal vasculitis, hemorrhages, and widespread pinpoint deposits in the peripheral retina. Two patients underwent vitrectomy with marked improvement of visual acuity postoperatively. Vitreous and serum samples for VEGF were analyzed with an enzyme-linked immunosorbent assay (ELISA). Forty-eight healthy adult volunteers were enrolled as a control group for the analysis of serum VEGF. Eight subjects who underwent vitrectomy for a macular epiretinal membrane or macular hole were enrolled as control for the analysis of vitreous VEGF. Both serum and vitreous VEGF levels of patients were raised compared to that of controls. Venous blood was collected from family members and the genomic DNA was extracted. All exons and exon-intron boundaries of the TTR gene were sequenced. A previously-described pathogenic transversion in exon 2 (c.G106C, p.Ala36Pro) was identified. Within this family eight individuals were confirmed as affected. In conclusion, a Chinese family with TTR Ala36Pro associated FTA is characterized by early ocular involvement. Widespread pinpoint lesions indicate RPE lesions caused by TTR deposition. FTA is associated with increased VEGF levels, both in serum and vitreous.

Phenotypic characterization of a Chinese family with autosomal dominant cone-rod dystrophy related to GUCY2D.

BACKGROUND: This study aimed to evaluate the clinical phenotype and investigate the molecular genetic defect in a Chinese family with autosomal dominant cone-rod dystrophy (ADCRD). METHODS: Family history was collected and patients underwent regular ophthalmologic examinations. Two affected individuals underwent three-year follow-ups to analyze the course of the disease. Venous blood was collected from family members and genomic DNA was extracted. A whole genome linkage analysis of 11 family members was performed using an Illumina Infinium Human Linkage-12 panel. All exons and exon-intron boundaries of guanylate cyclase 2D gene (GUCY2D) were sequenced for familial gene mutation. RESULTS: Decreased visual acuity and photophobia usually commenced in early childhood in these patients. The family demonstrated an age-dependent increase in macular abnormalities with progressive development of geographic atrophy. Electrophysiological testing revealed a marked loss of cone function. Initially, a genome-wide linkage analysis mapped the disease to chromosome 17 (1-36 cM), with a maximum LOD score of 1.505. Sequence analysis of the GUCY2D gene in the linkage interval detected a recurrent heterozygous mutation, c.2513G > C (p.R838P). This mutation appeared in all seven patients with ADCRD but did not appear in any of the four unaffected family members. CONCLUSIONS: A missense mutation in the GUCY2D gene caused ADCRD in this family. Clinical follow-up of this family with a typical CRD phenotype revealed disease progression during the time period.

[Factors associated with visual prognosis of acute retinal necrosis syndrome].

OBJECTIVE: To investigate relevant factors affecting the prognosis of acute retinal necrosis syndrome (ARN). METHODS: Case-series study. The clinical data of 41 patients (53 eyes) with ARN were retrospectively analyzed. Eyes were divided into two groups according to best corrected visual acuity at final visit. The groups were best corrected visual acuity better than 0.1 (group A, 28 eyes) and worse than 0.1 (group B, 25 eyes). Data were analyzed using the χ(2) test, Fisher exact test, Mann-Whitney test, bivariate correlation statistics, and multinomial logistic regression analysis. RESULTS: All patients were treated with systemic antivirus drugs and glucocorticoid. Ten eyes were treated with prophylactic laser retinopexy, 26 eyes underwent intravitreal ganciclovir, and 31 eyes underwent vitrectomy. All contralateral eyes of unilateral ARN patients were not involved after systemic antivirus treatment. Compared to group B (16.0%, 4/25), more eyes with best corrected visual acuity better than 0.1 at first visit were observed in group A (85.7%, 24/28) (χ(2) = 23.037, P = 0.000). Duration from onset of symptoms until first administration of antivirus drugs was shorter in group A [(15 ± 13) days] than in group B [(30 ± 34) days, Z = -2.414, P = 0.016]. Compared to group A (25.0%, 7/28; 10.7%, 3/28; 7.1%, 2/28; 39.3%, 11/28), more eyes in group B suffered from retinal detachment (80.0%, 20/25), occlusive central retinal vasculopathy (56.0%, 14/25), optic atrophy (36.0%, 9/25) and proliferative vitreoretinopathy (92.0%, 23/25) (χ(2) = 13.862, 10.440, 5.048, 13.749; P = 0.000, 0.001, 0.025, 0.000). Logistics regression analysis showed that visual prognosis were related to factors including best corrected visual acuity better at first visit (OR = 27.225, P = 0.003) and occlusive central retinal vasculopathy (OR = 0.065, P = 0.053). No difference in the number of eyes with increased intraocular pressure was observed between group A and group B (P > 0.05). Prophylactic laser retinopexy before retinal detachment and intravitreal ganciclovir were not associated with visual prognosis (P > 0.05). CONCLUSION: Worse visual acuity at first visit and occlusive central retinal vasculopathy are major relevant factors threatening visual prognosis.

Novel PRPF31 mutations associated with Chinese autosomal dominant retinitis pigmentosa patients.

PURPOSE: To identify the mutations in the pre-mRNA processing factor 31 homolog (PRPF31) gene in Chinese families with autosomal dominant retinitis pigmentosa (adRP) and to characterize the clinical features of those patients who were found to have mutations in the PRPF31 gene. METHODS: Detailed ocular examinations were performed, and genomic DNA was isolated by standard methods for genetic diagnosis. Probands from each family were screened for mutations in the PRPF31 gene that was known to cause adRP. Cosegregation analysis was performed in the available family members. Linkage analysis was performed for one missense mutation to calculate the likelihood of its pathogenicity. Two hundred unrelated, healthy Chinese subjects were screened to exclude nonpathogenic polymorphisms. RESULTS: Forty Chinese families with adRP were selected by an analysis of pedigrees. We identified four mutations (c.196_197delAA, c.544_618del75bp, c.615delC, and c.895T>C) in total, and three deletions were novel. Cosegregation analysis of the available family members (20 patients and 17 unaffected family members) revealed that each index patient and all affected family members showed a heterozygous mutation in the PRPF31 gene. In two families, incomplete penetrance was observed. Linkage analysis achieved the maximum LOD score of c.895T>C is 2.09, achieved at θ=0. The four probands with PRPF31 mutations showed classical signs of RP, with relatively preserved central vision and severe visual field constriction. CONCLUSIONS: Our studies extended the mutation spectrum of PRPF31, and mutations in PRPF31 were found at a relatively high frequency (10%, 4 of 40 adRP families) in our cohort.

Novel RPE65 mutations associated with Leber congenital amaurosis in Chinese patients.

PURPOSE: Retinal pigment epithelium-specific protein 65 kDa (RPE65) plays an essential role in vitamin A metabolism necessary for synthesizing the visual pigment 11-cis-retinal chromophore. Mutations in RPE65 cause the childhood blindness disorder known as Leber congenital amaurosis (LCA), as well as autosomal recessive retinitis pigmentosa (RP). The purpose of this study was to identify RPE65 mutations in Chinese patients with LCA, determine the prevalence of RPE65 mutations in this cohort, and assess the clinical features of those patients with RPE65 mutations. METHODS: Detailed ocular examinations were performed, and genomic DNA was isolated with standard methods for genetic diagnosis. All 14 exons of RPE65 were amplified with PCR and screened for mutation with direct DNA sequencing. Two hundred unrelated healthy Chinese subjects were screened to exclude nonpathogenic polymorphisms. Multiple alignments of eight eukaryotic RPE65 orthologs were performed. RESULTS: A total of 101 LCA patients, drawn from 100 unrelated families, were selected for mutation screening in the RPE65 gene. Compound heterozygous missense mutations Leu67Arg and Tyr368Cys were identified in two affected sisters and segregated with their family. Four previously reported polymorphisms were identified in this study. No other disease-related mutation was detected. The frequency spectrum of variations in the RPE65 gene was estimated to be 1% (1/100) in this cohort of Chinese patients with LCA. The two patients showed classical signs of LCA with relatively preserved central vision and retinal structure. CONCLUSIONS: The RPE65 mutation is a rare cause of LCA in the Chinese population. Compound heterozygous missense mutations Leu67Arg and Tyr368Cys are related to a relatively mild LCA phenotype. Genetic characterization of patients with RPE65 mutations is important for future rational therapies.

Genetic and phenotypic characteristics of three Mainland Chinese families with choroideremia.

PURPOSE: To describe the phenotype and genotype of three Mainland Chinese families affected by choroideremia (CHM). METHODS: Complete ophthalmic examinations were conducted in three unrelated Chinese families with CHM. Peripheral blood samples were collected from the families for genetic and immunoblot analysis. All exons and flanking intronic regions of the gene encoding Rab escort protein-1 (Rep-1) were amplified with PCR and screened for mutations with Sanger sequencing. The three-dimensional structure of mutated Rep-1 was modeled using sequence homology with rat proteins to analyze the effect of the mutation detected in one family. RESULTS: All affected males had characteristic signs and symptoms of CHM; however, central visual acuity impairment occurred earlier than expected. All female carriers older than 45 years had pigmentary changes, and one female carrier was symptomatic with vision loss. Three different mutations in Rep-1, c.1801-1G>A, c.1130 T>A, and c.612delAG, were detected in the three families. CONCLUSIONS: In Mainland Chinese families, the central visual acuity of male patients with CHM can be affected at an early age (second decade), whereas female CHM carriers may manifest signs and symptoms at a later age (≥ 45 years). One previously reported and two novel Rep-1 mutations were detected in three Chinese patients with CHM.

A novel splice site mutation in the COL4A5 gene in a Chinese female patient with rare ocular abnormalities.

PURPOSE: To describe an unusual ocular phenotype in a Chinese female patient with X-linked Alport syndrome (XLAS), and to characterize the type IV collagen alpha 5 (COL4A5) gene mutation in the patient and her son. METHODS: Detailed ophthalmologic examinations and optical coherence tomography were performed in the patient and her family members. For gene analysis of COL4A5, the entire coding region of COL4A5 mRNA from cultured skin fibroblast was analyzed by using reverse-transcription-polymerase chain reaction (RT-PCR) and direct sequencing, and genomic DNA was analyzed by using PCR and direct sequencing. RESULTS: The patient presented with progressive myopia at age 14 and bilateral giant macular holes (about 2 disc diameter) at age 28. At age 33 when presented to our hospital, slit lamp examination of the anterior segment showed bilateral anterior and posterior lenticonus; fundus photography and optical coherence tomography showed bilateral giant macular holes which were larger than photographed at age 28. Electron microscopy of renal biopsy showed irregular thinned and thickened areas of the glomerular basement membrane with splitting of the lamina densa. Her son was then found to have hematuria (at age 3), and indirect immunofluorescence of the epidermal basement membrane showed negative staining for the collagen α5(IV) chain. However, the ophthalmological examinations of her son were unremarkable. A novel COL4A5 mutation g. 4400_4400+1del, leading to an indel in exon 45 (r. 4198delins4198+2_ 4198+72), was detected in the patient and her son. This mutation produces a shift in the reading frame, resulting in a missense sequence of 13 codons followed by a premature stop codon. Her mother was not affected with the mutation. CONCLUSIONS: Our report extends the phenotypic and genotypic spectrum of X-linked Alport syndrome.

Cysteine-rich 61 (CYR61) is up-regulated in proliferative diabetic retinopathy.

BACKGROUND: To investigate the role of CYR61 as a retinal angiogenic factor in proliferative diabetic retinopathy (PDR). METHODS: Effects of CYR61 on RF/6A cell proliferation, migration and angiogenesis were observed by MTT assay, Transwell assay, and tube formation assay. The expression and distribution of CYR61 on retina layers of diabetic mouse were demonstrated by immunohistochemistry. The expression of Cyr61 mRNA in diabetic mouse retina was evaluated by reverse transcription-polymerase chain reaction (RT-PCR). Vitreous CYR61 levels of PDR and non-diabetic patients were measured by enzyme-linked immunosorbent assay (ELISA). Expression and distribution of CYR61 on epiretinal membrane of PDR, proliferative vitreoretinopathy (PVR) and idiopathic epiretinal membrane were evaluated by immunohistochemistry. RESULTS: RF/6A cell proliferation, migration and tube formation capacity increased with increased concentration of CYR61 (p = 0.000). Anti-CYR61 antibody could inhibit cell migration and tube formation promoted by CYR61. In diabetic mouse, CYR61 was expressed in retina layers just as normal mouse, but the staining was stronger than normal in ganglion cell layer and inner plexiform layer. The Cyr61 mRNA expression in retina of diabetic mouse was more than that in normal mouse (p = 0.009). Vitreous CYR61 level was higher in patients with PDR than non-diabetic patients (p = 0.000). PDR patients with plenty of neovasculature on retina and epiretinal membranes had higher level of vitreous CYR61 than patients with little neovasculature (p = 0.001). CYR61 expressed in the cytoplasm of epiretinal membranes in PDR, especially in the wall cells of the tube-like structure. CONCLUSIONS: CYR61 are likely to be involved in the pathogenesis of diabetic retinopathy, and may play a role in the course of neovasculation.

Locally produced insulin-like growth factor-1 by orbital fibroblasts as implicative pathogenic factor rather than systemically circulated IGF-1 for patients with thyroid-associated ophthalmopathy.

BACKGROUND: To determine the correlation between clinical activity scores (CAS) of thyroid-associated ophthalmology (TAO) patients and their locally produced and/or systemically circulating insulin-like growth factor-1 (IGF-1), and to assess the possible pathogenic role of IGF-1 in TAO. METHODS: Eighteen patients with TAO, and 16 age- and gender-matched controls were included in the present study. Among them, orbital tissue surgically collected from five TAO patients and five healthy controls was used for orbital fibroblasts (OFs) culture and in vitro study. Total and free IGF-1 in serum levels were determined by an ELISA kit for all the participants in this study. The IGF-1 concentration in culture media of OFs was determined using a noncompetitive time-resolved radioimmunoassay kit. The effect of octreotide (OCT), a somatostatin analog, on proliferation of OFs was assessed using the MTT assay. IGF-1 mRNA levels were measured by real-time polymerase chain reaction (PCR). RESULTS: Cultured OFs from both TAO patients and normal donors secreted IGF-1, and the secretion continued over a 72 hour period in vitro. IGF-1 secretion by OFs was elevated in the TAO group. Both the elevated secretion of IGF-1 and proliferation of OFs from TAO patients could be inhibited by OCT. Result of quantitative PCR showed that IGF-1 mRNA expression by OFs in TAO patients was up-regulated more than 2-fold compared with normal controls (P < 0.05), and this up-regulation was prevented by OCT treatment. Total and free serum IGF-1 levels in TAO patients were similar to those of normal controls. However, the IGF-1 level in cultured medium of OFs from TAO patients, but not serum levels of IGF-1, was positively correlated with CAS (r = 0.97, P = 0.017). CONCLUSIONS: Local production of IGF-1 by cultured OFs may be positively correlated with CAS, whereas systemically circulating IGF-1 may remain unchanged in TAO patients. Thus, locally produced IGF-1 may develop a role in the pathogenesis of TAO in an autocrine or paracrine fashion. The inhibitory effect of OCT on proliferating and IGF-1 mRNA levels of cultured OFs from TAO patients may be used as the mechanistic explanation for somatostatin analog as a valuable option in the treatment of TAO.

Mycobacterium massiliense keratitis.

PURPOSE: The aim of this study is to report a case of keratitis caused by Mycobacterium massiliense, which is a subtype of non-tuberculous mycobacteria. METHODS: A 23-year-old Chinese man with a history of metal corneal foreign body removal was diagnosed with keratitis of his right eye 4 days after corneal trauma. He presented with intractable redness and continued corneal lesion with further vision loss after 2 weeks of conventional therapy. Pathogen testing and drug susceptibility testing were done. RESULTS: Corneal scraping and culture showed acid-fast staining positive bacilli. Polymerase chain reaction and sequencing confirmed that it was M. massiliense. The corneal ulcer was ultimately cured with 2 months treatment of amikacin and levofloxacin according to antibiotic susceptibility tests. CONCLUSIONS: Based on this case, multiple gene sequencing is required for identification of M. massiliense. Early diagnosis and prompt treatment will minimize the risk of sequelae, such as corneal scar and neovascularization.

Spectral-domain optical coherence tomography characteristics of macular contusion trauma.

PURPOSE: To describe the characteristics of macular lesions after eye trauma using spectral-domain optical coherence tomography (OCT). METHODS: We retrospectively reviewed and described 2-dimensional (2D) and 3-dimensional (3D) spectral-domain OCT characteristics of 24 consecutive eyes of 24 cases that were identified with macular lesions after eye trauma. RESULTS: Spectral-domain OCT clearly demonstrated a variety of lesions: hemorrhage, epiretinal membrane formation, macular hole, retinal pigment epithelium (RPE) rupture combined with choroidal neovascularization formation, photoreceptor inner/outer surface changes, RPE detachment, scar formation with e.g. diffuse macular edema, macular distortion or macular atrophy. Main lesions were located in the fovea area in 11 eyes (45.8%), the parafovea in 3 eyes (12.5%) and the whole macular area in 10 eyes (41.7%). CONCLUSION: Spectral-domain OCT is a useful investigation providing refined and credible 2D/3D images, precisely locating macular lesions after contusion trauma.

Spectral domain optical coherence tomography of Vogt-Koyanagi-Harada disease: novel findings and new insights into the pathogenesis.

OBJECTIVE: To provide novel spectral domain optical coherence tomography (SD OCT) findings of Vogt-Koyanagi-Harada (VKH) disease as well as new insights into the pathogenesis of this disease. METHODS: Detailed SD OCT and fluorescein angiography (FA) findings of 18 consecutive VKH patients (11 women and 7 men) from December 2007 to April 2009 who were in acute uveitic stage at presentation were reviewed. All the patients had been followed up for at least 6 months with reevaluation(s) of SD OCT performed in 10 patients. RESULTS: Intraretinal cysts were found to be located in various layers of the outer retina. In addition to the photoreceptor layer, they could also be found between the outer plexiform layer and the outer nuclear layer, or spanning the external limiting membrane. On FA, intraretinal cysts could be hypofluorescent, normofluorescent, or hyperfluorescent. Some intraretinal cysts had a characteristic FA pattern, in which a small round hypofluorescent area was surrounded by a ring of hyperfluorescence (donut-shaped dye pooling). Subretinal fibrinoid deposit appeared in acute uveitic stage in two severe VKH patients and seemed to develop from subretinal exudates and evolved into typical subretinal fibrosis. Gradual transfiguration/migration and progressive proliferation/pigmentation of the subretinal fibrinoid deposit/subretinal fibrosis was observed in one patient. CONCLUSIONS: Intraretinal cysts could form in various layers of the outer retina and may result from extension of choroidal inflammation. Subretinal fibrosis may develop from subretinal exudates in VKH patients and may cause substantial visual impairment.