Min Wang

Effect of preoperative retinal sensitivity and fixation on long-term prognosis for idiopathic macular holes

BackgroundTo study the roles of preoperative retinal sensitivity and fixation exams in predicting the long-term prognosis of idiopathic macular hole (IMH) patients after successful vitrectomy.MethodsA total of 39 IMH patients (39 eyes) were included in this prospective cohort case series study. Twenty-three gauge pars plana vitrectomy was performed on each patient. Results of best-corrected visual acuity (BCVA), macular hole diameter, MP − 1 microperimetry (MP − 1) tests, and continuity of the photoreceptor inner and outer segment (IS/OS) junction were recorded for analysis.ResultsPostoperative BCVA at 12 months was significantly correlated with macular hole diameters (p < 0.05), preoperative BCVA (p = 0.020), mean retinal sensitivity (p < 0.001), and fixation location percentage (p < 0.001). However, merely preoperative mean retinal sensitivity (r = 0.5448, p < 0.001) and fixation location percentage (r = 0.5624, p < 0.001) were suggested to be quantitatively predictive for the visual prognosis by multiple stepwise linear regression analysis. Moreover, patients that had smaller hole sizes (p < 0.01), better mean retinal sensitivity (p = 0.003), higher fixation quality scores, and higher fixation location percentage (p = 0.008) before surgery were prone to get continuous IS/OS junction 12 months after surgery.ConclusionsMP-1 exams evaluate the dysfunctional hole margin and thus provide more comprehensive information of the preoperative visual function of IMH patients. Both mean retinal sensitivity and fixation behaviors are ideal measurements in predicting the prognosis after successful macular hole surgery.

Retinal Nerve Fiber Layer Analysis with Scanning Laser Polarimetry and RTVue-OCT in Patients of Retinitis Pigmentosa

Purpose: To measure the thickness of the retinal nerve fiber layer (RNFL) of patients with retinitis pigmentosa (RP) and that of normal controls by scanning laser polarimetry with enhanced corneal compensation (GDxECC) and RTVue-optical coherence tomography (OCT). Methods: Fifty-two eyes of 26 patients were included. All patients underwent complete ophthalmological examinations and testing with GDxECC. Twenty-eight of 52 eyes of RP patients underwent RTVue-OCT measurements. A group of 50 eyes of 25 normal subjects (controls) was also included. GDxECC measured RNFL thickness in the peripapillary area in all subjects as well as temporal-superior-nasal-inferior-temporal (TSNIT) parameters, including TSNIT means, superior and inferior region means, TSNIT standard deviation (SD), inter-eye symmetry and nerve fiber indicator (NFI). RTVue-OCT measured the mean, superior, inferior, temporal and nasal quadrant RNFL thickness. Result: In RP patients and controls, TSNIT means by GDxECC were, respectively, 65.00 ± 7.35 and 55.32 ± 5.20. Mean superior quadrant thicknesses were80.56 ± 10.93 and 69.54 ± 7.45. Mean inferior thicknesses were 80.58 ± 9.34 and 69.12 ± 7.78. SDs were 27.92 ± 5.21 and 28.23 ± 4.01. Inter-eye symmetries were 0.82 ± 0.17 and 0.87 ± 0.09. NFIs were 9.74 ± 8.73 and 16.81 ± 8.13. The differences between mean TSNIT, mean superior and mean inferior quadrant thicknesses and NFIs were statistically significant (p < 0.001). In RTVue-OCT measurements, the differences between mean, superior, inferior and temporal quadrant RNFL thicknesses were statistically significant (p = 0.0322, 0.0213, 0.0387, 0.0005). Conclusions: The RNFL measured by GDxECC was significantly thicker in RP patients than in controls. RNFL thickness measured by RTVue-OCT was significantly greater in RP patients than in controls in the superior, inferior and temporal regions. This contribution provides information on RNFL thickness and discusses the mechanism underlying this phenomenon.

Quercetin Declines Apoptosis, Ameliorates Mitochondrial Function and Improves Retinal Ganglion Cell Survival and Function in In Vivo Model of Glaucoma in Rat and Retinal Ganglion Cell Culture In Vitro

Glaucoma is a progressive neuropathy characterized by the loss of retinal ganglion cells (RGCs). Strategies that delay or halt RGC loss have been recognized as potentially beneficial for rescuing vision in glaucoma patients. Quercetin (Qcn) is a natural and important dietary flavonoid compound, widely distributed in fruits and vegetables. Mounting evidence suggests that Qcn has numerous neuroprotective effects. However, whether Qcn exerts neuroprotective effects on RGC in glaucoma is poorly understood. In this study, we investigated the protective effect of Qcn against RGC damage in a rat chronic ocular hypertension (COHT) model in vivo and hypoxia-induced primary cultured RGC damage in vitro, and we further explored the underlying neuroprotective mechanisms. We found that Qcn not only improved RGC survival and function from a very early stage of COHT in vivo, it promoted the survival of hypoxia-treated primary cultured RGCs in vitro via ameliorating mitochondrial function and preventing mitochondria-mediated apoptosis. Our findings suggest that Qcn has direct protective effects on RGCs that are independent of lowering the intraocular pressure (IOP). Qcn may be a promising therapeutic agent for improving RGC survival and function in glaucomatous neurodegeneration.

Asiatic Acid Prevents Retinal Ganglion Cell Apoptosis in a Rat Model of Glaucoma

Asiatic acid (AA), a pentacyclic triterpene derived from the tropical medicinal plant Centella asiatica, has been widely used as an antioxidant and anti-inflammatory agent. Evidence regarding the neuroprotective properties of AA is emerging. However, the protective effects of AA and its mechanism in glaucoma are poorly understood. In the current study, we investigate the neuroprotective effect and mechanism of AA on retinal ganglion cells (RGCs) in a rat model of glaucoma. Elevated intraocular pressure (IOP) was induced in adult rats by injecting microspheres into the anterior chamber. AA was intravitreally injected into glaucomatous rats. RGC densities were analyzed by evaluating surviving RGC number of the retinal flatmounts and retinal sections, and the apoptotic cell number were evaluated by analyzing retinal sections. RGC function was assessed by measuring the photopic negative response (PhNR). Retinal Bcl-2, Bax, and cleaved caspase-3 expression were determined using a Simple Western System, real-time PCR and immunofluorescence staining. AA reduced the loss of RGCs and decreased the apoptotic RGC number. AA exerted neuroprotective effects and ameliorated retinal dysfunction in impaired RGCs in a rat model of glaucoma. AA protected RGCs by upregulating the expression of the antiapoptotic protein Bcl-2 and downregulating the expression of the pro-apoptotic proteins Bax and caspase-3. This study has provided important evidence indicating that AA may be a potential therapeutic agent for glaucoma.

Comparative analysis of retinal ganglion cell damage in three glaucomatous rat models

ABSTRACT Progressive retinal ganglion cell (RGC) death is the major cause of retinal nerve fiber layer thinning and visual field defects in glaucoma. The purpose of this study was to compare RGC damage in three commonly used glaucomatous rat models. These models were generated by (i) injection of paramagnetic microbeads into the anterior chamber; (ii) cauterization of three episcleral veins of the eye (EVC); and (iii) intravitreal injection of N‐Methyl‐D‐Aspartate (NMDA). Intraocular pressure (IOP) was measured with a rebound tonometer at 6, 12, and 18h; 1, 3, and 5 days; and 1, 2, 3, 4, 6, and 8 weeks. We measured the RGC density of the three glaucomatous models in the flat‐mounted retina by immunofluorescence. Subsequently, the thicknesses of both retinal ganglion cell layer (GCL) and inner retinal layer (IRL) were analyzed by hematoxylin and eosin staining of retinal sections. The visual functional deterioration was evaluated by measurement of the photopic negative response (PhNR) of different models. The IOP averages during three weeks were 22.35±1.23mmHg (mean±SD), 20.91±1.97mmHg, and 9.67±0.42mmHg, with 50.2%, 44.00% and 66.76% RGC loss by 8 weeks, respectively, in the microbead group, EVC group and NMDA group. Decreased thickness in the GCL was observed in all three groups, while the thickness of IRL and ONL was decreased in the EVC and NMDA groups. Significant positive correlation of RGC loss rate with &Dgr;IOP integral were demonstrated in both microbead and EVC models. Moreover, we found that the PhNR amplitudes declined early by the first day in the NMDA group, 5 days later in the EVC group and by 7 days in the microbead group. Each glaucomatous rat model has its strength and weakness. Our study provides detailed data for choosing suitable animal models to advance glaucoma research. HIGHLIGHTSGlaucomatous models were established by microbead; NMDA injection and EVC.Changes of IOP; RGC count and retinal thickness were analyzed in three models.Visual function impairment measured by PhNR differed in glaucomatous models.

Retinal displacement after closure of idiopathic macular hole

Objective: To study the foveal displacement during the closure of idiopathic macular holes (MHs). Methods: Thirty-seven idiopathic MH patients treated by pars plana vitrectomy and internal limiting membrane peeling were studied prospectively. Locations of MH center and foveal pit were measured by optic coherence tomography. Retinal displacement was observed using confocal scanning laser ophthalmoscopy. Results: A total of 40 eyes were included in this study and MHs were closed in 37 eyes (92.5%). The confocal scanning laser ophthalmoscopy showed that all of the retinal capillaries in the superior, inferior, nasal and temporal sides of the MHs moved toward the optic nerve head (ONH). The optic coherence tomography results showed that the mean nasal displacements of foveal pits were (102.9±61.2), (109.6±53.1), and (137.0±52.0) μm at 3, 6 and 12 months, respectively. And the mean vertical displacements were (55.9±49.4), (61.4±57.8) and (67.8±54.3) μm, respectively. Post-operative foveal pits were located in the nasal side of the MH centers. The extension of retina and nasal to the MH were in opposite directions: the nasal hole margin moved toward the MH, but the retina located closer to the ONH moved toward the ONH. The fellow eyes of three patients developed into idiopathic MH during the follow-up period and operations were performed for all of the three patients. Conclusion: Our results showed that center of macula does not move when an idiopathic MH develops, but it moves toward ONH during closure of hole; thus, new fovea is in nasal side of original fovea.

Next-Generation Sequencing-Aided Rapid Molecular Diagnosis of Occult Macular Dystrophy in a Chinese Family

Purpose: To show early, rapid and accurate molecular diagnosis of occult macular dystrophy (OMD) in a four-generation Chinese family with inherited macular dystrophy. Methods: In the current study, we comprehensively screened 130 genes involved in common inherited non-syndromic eye diseases with next-generation sequencing-based target capture sequencing of the proband of a four-generation Chinese family that has suffered from maculopathy without a definitive diagnosis for over 10 years. Variants were filtered and analyzed to identify possible disease-causing variants before validation by Sanger sequencing. Results: Two heterozygous mutations—RP1L1 c.133 C > T (p.Arg45Trp), which is a hot spot for OMD, and ABCA4 c.6119 G > A (p.Arg2040Gln), which was identified in Stargardt’s disease were found in three patients, but neither of the mutations was found in the unaffected individuals in the same family, who are phenotypically normal or in the normal control volunteers. Conclusion: These results cannot only confirm the diagnosis of OMD in the proband, but also provide presymptomatic diagnosis of the proband’s children before the onset of visual acuity impairment and guidance regarding the prognosis and management of these patients. Heterozygous mutations of RP1L1 c.133 C > T (p.Arg45Trp) and ABCA4 c.6119 G > A (p.Arg2040Gln) are likely responsible for OMD. Our results further extend our current understanding of the genetic basis of OMD, and emphasize the importance of molecular diagnosis and genetic counseling for OMD.

Novel compound heterozygous mutations in CNGA1in a Chinese family affected with autosomal recessive retinitis pigmentosa by targeted sequencing

BackgroundAbout 37 genes have been reported to be involved in autosomal recessive retinitis pigmentosa, a hereditary retinal disease. However, causative genes remain unclear in a lot of cases.MethodsTwo sibs of a Chinese family with ocular disease were diagnosed in Eye and ENT Hospital of Fudan University. Targeted sequencing performed on proband to screen pathogenic mutations. PCR combined Sanger sequencing then performed on eight family members including two affected and six unaffected individuals to determine whether mutations cosegregate with disease.ResultsTwo affected members exhibited clinical features that fit the criteria of autosomal recessive retinitis pigmentosa. Two heterozygous mutations (NM000087, p.Y82X and p.L89fs) in CNGA1 were revealed on proband. Affected members were compound heterozygotes for the two mutations whereas unaffected members either had no mutation or were heterozygote carriers for only one of the two mutations. That is, these mutations cosegregate with autosomal recessive retinitis pigmentosa.ConclusionsCompound heterozygous mutations (NM000087, p.Y82X and p.L89fs) in exon 6 of CNGA1are pathogenic mutations in this Chinese family. Of which, p.Y82X is firstly reported in patient with autosomal recessive retinitis pigmentosa.

Structural and functional changes after surgical treatment in foveoschisis: a case report

Macular abnormalities with distorted vision are not common in children and young adults. X-linked retinoschisis (XLRS) is the leading cause of juvenile macular degeneration. It is the result of mutations of the RS1 gene in Xp22.1 in males. It is characterised by splitting of the inner retina, primarily in the nerve fibre layer but may extend to other layers, including the outer retina. The pathophysiology is not fully understood but suspicion falls on Müller cells.