Analysis of Phenotypes Associated with Deficiency of PAX6 Haplotypes in Chinese Aniridia Families.

OBJECTIVE: To examine the clinical phenotype and genetic deficiencies present in Chinese aniridia families with PAX6 haplotype deficiency. METHODS: A comprehensive questionnaire and ophthalmological assessments were administered to both affected patients and unaffected relatives. The clinical feature analysis included the evaluation of visual acuity, intraocular pressure, slit-lamp anterior segment examination, fundus photography, and spectral domain optical coherence tomography. To identify the mutation responsible for aniridia, targeted next-generation sequencing was used as a beneficial technique. RESULTS: A total of 4 mutations were identified, consisting of two novel frameshift mutations (c.314delA, p.K105Sfs*33 and c.838_845dup AACACACC, p.S283Tfs*85), along with two recurring nonsense mutations (c.307C>T, p.R103X and c.619A>T, p.K207*). Complete iris absence, macular foveal hypoplasia, and nystagmus were consistent in these PAX6 haplotype-deficient Chinese aniridia families, while corneal lesions, cataracts, and glaucoma exhibited heterogeneity both among the families and within the same family. CONCLUSION: In our study, two novel PAX6 mutations associated with aniridia were identified in Chinese families, which expanded the phenotypic and genotypic spectrum of PAX6 mutations. We also analyzed the clinical characteristics of PAX6 haplotype deficiency in Chinese aniridia families.

Traumatic dislocation of the iris into the vitreous cavity with intact lens: a case report.

BACKGROUND: Traumatic aniridia occurs when the iris is extruded from the eye and is often accompanied by lens injuries. However, traumatic aniridia due to dislocation of the iris into the vitreous cavity without lens damage has never been reported. CASE PRESENTATION: A 30-year-old man presented with visual loss and pain for 6 h after a thin wire injured his right eyeball. Ophthalmologic examinations manifested a 2 mm full-thickness corneal laceration and total hyphema. An intact clear lens, healthy attached retina, and almost complete iris tissue in the vitreous cavity were found after resolution of hyphema the next day. Further examination revealed that the defect in the zonule below the corneal wound was the path for the iris to enter the vitreous cavity. The patient opted for nonsurgical treatment until pigment granules and opacity were observed in the vitreous cavity after 50 days. Vitrectomy was performed to remove the dislocated iris. CONCLUSIONS: The presentation of this unique case indicates that the torn iris was displaced to the vitreous cavity with an intact lens and missing local zonula instead of out the corneal laceration after a penetrating injury. The type of injury, mechanism, and force on the spot may contribute to the occurrence of this rare condition. Instead of artificial irises, tinted glasses were more appropriate treatment option for this patient. Peripheral retinal examination was essential in the management of this case. In such cases, the iris in the vitreous cavity should be resected to prevent complications.

Various phenotypes of autosomal dominant cone-rod dystrophy with cone-rod homeobox mutation in two Chinese families.

AIM: To present the clinical manifestations of 5 autosomal dominant cone-rod dystrophy (adCORD) patients from two Chinese families with cone-rod homeobox (CRX) mutation (p.R41W), and to explore the clinical heterogeneity of adCORD with CRX mutation (p.R41W). METHODS: Interrogation and ophthalmological examinations were undertaken in all patients and unaffected members. Analysis of clinical features was performed by visual acuity, slit lamp examination, visual field examination, fundoscopy, autofluorescence and spectral domain optical coherence tomography. Targeted next-generation sequencing was applied as a useful tool to identify the causative mutation of CORD genes. RESULTS: A CRX missense mutation c.121C>T was identified in all patients, resulting in an amino acid change from arginine acid to tryptophan (p.R41W). The patients presented with early onset, progressive and different severities with CORD. CONCLUSION: This is the first report of the clinical phenotype of CRX mutation (p.R41W) in Chinese families, and the mutation can lead to a wide range of various retinal phenotypes.

Novel mutations in the BEST1 gene cause distinct retinopathies in two Chinese families.

AIM: To describe the clinical heterogeneity of patients with novel mutations in BEST1. METHODS: All the members in the two Chinese families underwent detailed clinical evaluations including best-corrected visual acuity, slit-lamp examination, applanation tonometry, and dilated fundus examination. Fundus autofluorescence, fundus fluorescein angiography, spectral-domain optical coherence tomography, electrooculography, and electroretinogram were also performed. Genomic DNA was extracted from venous blood for all the participants. The targeted next-generation sequencing of inherited retinal disease-associated genes was conducted to identify the causative mutation. RESULTS: A novel BEST1 missense mutation c.41T>C (p.Leu14Ser) was identified in Family 1. It was co-segregated with the phenotype of best vitelliform macular dystrophy (BVMD) and bioinformatics analysis confirmed it was harmful. Another novel BEST1 frameshift mutation c.345_346insGGCAAGGACG (p.Glu119Glyfs*116) and a novel USH2A missense mutation c.12560G>A, p.Arg4187His were identified in family 2 with retinitis pigmentosa (RP), which might interact and lead to the phenotype of RP. CONCLUSION: Two novel mutations in the BEST1 gene in two unrelated families with distinct phenotypes and BEST1 mutation accompanied with USH2A mutation would result in RP, which could be enormously helpful in understanding the pathogenesis of the inherited retinal disease caused by a BEST1 mutation.

A novel mutation of FOXC1 in a Chinese family with Axenfeld-Rieger syndrome.

Axenfeld-Rieger syndrome (ARS) is a disorder affecting the anterior segment of the eye and causing systemic malformations, and follows an autosomal-dominant inheritance pattern. The aim of the present study was to identify the underlying cause of ARS in a Chinese family. Genomic DNA was extracted from the peripheral blood of the subjects from a family with ARS. The pathogenic variant was identified by targeted next-generation sequencing and confirmed by Sanger sequencing. A novel heterozygous mutation of the forkhead box (FOX)C1 gene (c.1494delG, p.G499Afs*20) was detected in all affected members of the family, while no mutation was identified in the unaffected members or in the 150 normal controls. The affected members exhibited typical ocular and craniofacial anomalies. The results of the present study demonstrated that a novel deletion in exon 1 of the FOXC1 gene caused ARS in this Chinese family.

A new perspective for analyzing clinical characteristics of idiopathic retinal vasculitis, aneurysms, and neuroretinitis syndrome.

PURPOSE: We aimed to analyze the clinical characteristics of idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome. Furthermore, we aimed to correlate the number and location of retinal aneurysms with the size of retinal non-perfusion area and neovascularization. METHODS: Six patients with IRVAN syndrome (1 male and 5 females, age 5-38 years) were enrolled in this study. Fundus fluorescein angiography (FFA) was used to determine the total number of retinal aneurysms, number of aneurysms within the first branch of the retinal artery, minimum distance between the non-perfusion margin and the optic disc, and the number of retinal aneurysms in each quadrant, as well as the type of neovascularization. RESULTS: The size of the non-perfusion area was positively correlated with the total number of retinal aneurysms, the number of aneurysms within the first branch of the retinal artery, and the number of retinal aneurysms in each quadrant (P < 0.05). During the 5-year follow-up, one patient exhibited a dynamic change in the number and location of retinal aneurysms. CONCLUSIONS: In IRVAN syndrome, the number and location of retinal aneurysms correlate with the size of retinal non-perfusion area and type of neovascularization.

Recombination and identification of human alpha B-crystallin.

AIM: To recombine the human alpha B-crystallin (αB-crystallin) using gene cloning technology and prokaryotic expression vector and confirm the biological activity of recombinant human αB-crystallin. METHODS: Cloning the human αB-crystallin cDNA according to the nucleotide sequence of the human αB-crystallin, constructing the pET-28/CRYAB prokaryotic expression plasmid by restriction enzyme digestion method, and stably expressing transformed into the Escherichia coli (E. coli) DH5 alpha. The recombinant human αB-crystallin was purified by Q sepharose. By enzyme digestion analysis, Western blotting and sequencing, the recombinant human αB-crystallin was identified and the activity of its molecular protein was detected. RESULTS: Compared with the gene bank (GeneBank), the cloned human sequence of human αB-crystallin cDNA has the same open reading frame. Identification and sequencing of the cloned human αB-crystallin cDNA in prokaryotic expression vector confirmed the full length sequence, and the vector was constructed successfully. The E. coli containing plasmid pET-28/CRYAB induced by isopropyl-ß-D-thiogalactoside successfully expressed the human αB-crystallin. Insulin confirmed that the recombinant human αB-crystallin has a molecular chaperone activity. CONCLUSION: The prokaryotic expression vector pET-28/CRYAB of recombinant human αB-crystallin is successfully constructed, and the recombinant human αB-crystallin with molecular chaperone activity is obtained, which lay a foundation for the research and application of the recombinant human αB-crystallin and its chaperone activity.

[Contrast Enhanced T2 Fluid-attenuated Inversion Recovery Imaging in Diagnosing Macular Edema Caused by Retinal Vein Occlusion:Report of One Case].

Conventional contrast-enhanced T1WI is a useful tool for evaluating the choroid but can not be used to evaluate the retina due to its small blood supply. Contrast-enhanced T2 fluid-attenuated inversion recovery imaging(CE-T2FLAIR)is sensitive to low-concentration MRI contrast;however,its role in the diagnosis of macular edema has not been described. A patient with macular edema caused by retinal vein occlusion was diagnosed by CE-T2FLAIR in the Hainan Branch of Chinese PLA General Hospital from July 20,2017 to August 4,2017,and our findings confirmed that CE-T2FLAIR could provide valuable imaging evidence for the diagnosis and evaluation of macular edema.

Early Diagnosis of Recurrent Optic Neuritis Using Contrast-Enhanced T2 Fluid-attenuated Inversion Recovery Imaging: a Case Report.

The diagnosis of the recurrent optic neuritis is commonly established clinically, and sometimes it could be challenging because the involved optic nerve does not always show significant enhancement on conventional contrast enhanced-T1 weighted imaging (CE-T1WI). In this paper, we reported a middle-aged female with early diagnosis of recurrent optic neuritis using contrast-enhanced T2 fluid-attenuated inversion recovery imaging (CE-T2FLAIR). The involved optic nerve presented evident enhancement on CE-T2FLAIR and no enhancement on CE-T1WI. This case suggested that the CE-T2FLAIR may be a useful diagnostic tool specifically for the recurrent optic neuritis in clinical practice.

Calibration and standardisation of graded optic nerve injuries in rats.

OBJECTIVES: To calibrate and standardise an animal model of graded optic nerve injury (ONI) in rats to facilitate future inter-laboratory data comparisons, focussing on quantification of injury intensity, injury severity, and the correlation between them. METHODS: A pair of cross-action forceps or a pair of artery clips was used to induce optic nerve (ON) crush injuries. A lever principle and a simplified method were used to measure the crushing force. The simplified method directly measured weights as an external force exerted on the tip of the forceps or clips, which was just sufficient to maintain a gap and was equivalent to the closing (crush) force. The impulse and averaged impulse were explored as physical quantities to compare injury intensities. Graded ONIs were made by crushing the ON for 3, 6, 12, 30 or 60 seconds by the cross-action forceps, or 5, 10 or 15 seconds by the artery clips. The injury severity was evaluated by counting surviving retinal ganglion cell (RGC) through applied FluoroGold to the superior colliculus and lateral geniculate body before ON crush, intact RGC counting by applied FluoroGold after ON crush, and ON axon counting. RESULTS: Similar results were obtained by the lever principle method and the simplified method. The crushing force of the cross-action forceps and the artery clips was 148.0 gram force (gf) and 32.4 gf, respectively. The graded ONI animal models were successfully created in rats without retinal ischaemia post-trauma. The averaged impulse produced by the artery clips for 15 seconds was equal to that produced by a 3-second crush of the cross-action forceps. The correlation between injury intensity and injury severity was fitted for a power function. DISCUSSION: Our results provide a simplified and effective means to quantify and analyse data from ON crush studies compared with previously reported animal models.

Pigmented paravenous retinochoroidal atrophy (Review).

Pigmented paravenous retinochoroidal atrophy (PPRCA) is an uncommon disease characterized by perivenous aggregations of pigment clumps associated with peripapillary and radial zones of retinochoroidal atrophy that are distributed along the retinal veins. Patients are usually asymptomatic and the disease process is non-progressive or slow and subtly progressive. It is commonly bilateral and symmetric. The cause of the condition may be unknown or idiopathic, although a dysgenetic, degenerative, hereditary etiology or even an inflammatory cause has been hypothesized. A non-inflammatory cause is referred to as primary, while inflammation-associated PPRCA is referred to as secondary or pseudo PPRCA. The present study reviewed and summarized the features of PPRCA.

Clinical characteristics of nonglaucomatous optic disc cupping.

Pathological optic disc cupping (ODC) is predominantly referred to as glaucoma; however, it is not only glaucoma that leads to pathological optic disc excavation. A number of other nonglaucomatous diseases also result in optic atrophy and excavation of the optic disc. Therefore, in the present study, the etiology of nonglaucomatous optic disc cupping (NGODC) was analyzed and differentiated from glaucomatous optic disc cupping (GODC). The morphology and clinical data of 19 eyes, from 12 patients exhibiting NGODC, were analyzed. Of the 12 cases, none were diagnosed with glaucoma, four presented with optic neuritis, one with Devic's disease, one with Leber's hereditary optic neuropathy, two with pituitary adenoma, one with basal ganglia cerebral hemorrhage, one with cilioretinal artery occlusion associated with central retinal vein occlusion, one with central retinal artery occlusion and the remaining patient exhibited optic nerve injuries. The key features that differentiated NGODC from GODC were the color of the optic disc rim and the correlation between visual field defects and the disc appearance. The focally notched disc also aided in distinguishing between the two disorders. The results of the present study indicated that it is critical to acknowledge that nonglaucomatous diseases also lead to ODC and that distinguishing between them is necessary.

[Clinical characteristics of paraneoplastic retinopathy and optic neuropathy].

OBJECTIVE: To analyze the clinical characteristics of paraneoplastic retinopathy and optic neuropathy(PRON). METHODS: Case series study. Eight patients were enrolled from October 2006 to March 2012 visited in ophthalmology department, the People Liberation Army General Hospital. The patients were underwent a series of examinations, including fundus photography, visual electrophysiology, fundus fluorescein angiography, optic coherent tomography,fundus autofluorescent imaging, perimetry, ultrasonography, magnetic resonance imaging, spinal tap and cerebrospinal fluid test, paraneoplastic syndrome (PNS) antibody test. The patients were followed up in outpatient department and(or) by phone. The clinical manifestation,entity types, and treatment were analyzed. RESULTS: Of the eight patients, there were cancer associated retinopathy(CAR) 3 cases, bilateral diffuse uveal melanocytic proliferation (BDUMP) 2 cases and paraneoplastic optic neuropathy(PON) 3 cases. Five patients were detected the PNS antibodies and revealed three patients with positive results. As for the primary malignancy,four of the eight patients were lung carcinoma,others included invasive thymoma, kidney cancer, acute lymphocytic leukemia and cervical cancer, each for one case. All the patients complained vision blurring or progressive visual decrease. Other complaints included dark shadow in two patients, shimmering, dazzling, double vision and eye pain, each in one patient. One patient complained progressive decreased vision in both eyes prior to the diagnosis of lung cancer. Of the 16 eyes of the eight patients, there were six patients with no light perception vision, five from light perception to 0.05, and other five with no less than 0.4 vision, in the end of the follow up. Five patients were treated with steroid with unsatisfactory efficacy. CONCLUSIONS: Each entity of PRON has its own clinical characteristics. PRON especially BDUMP may be a pre-metastatic disease.

[Outcome after treatment of myopia with implantable Collamer lens].

OBJECTIVE: To evaluate the efficacy, predictability, stability, and safety of the surgical correction myopia using implantable Collamer lenses (ICL) in phakic eyes. METHODS: A prospective study was performed to analyze 91 eyes of 48 patients who had the implantation of ICL for the treatment of myopia from July 2008 to February 2010. Patients were examined preoperatively and followed at 1 week, 1, 3, 6, and 12 months postoperatively. The examinations included the uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), refraction, contrast sensitivity, wavefront aberration, intraocular pressure, space between crystal lens and intraocular lens (vault), endothelial cell density (ECD), anterior chamber depth (ACD), surgical complication, etc. RESULTS: Successful implantation was achieved in all patients. The mean follow-up time was (9.54 ± 4.12) months (SD)(range 1 to 12 months). The mean preoperative SE was -12.38 diopters (D) (range -5.0D to -23.0D). Postoperatively, UCVA was maintained or improved in all eyes. UCVA achieved 1.0 in 58 eyes (64%) and BCVA gained more than 1 line in 69 eyes (75.9%). The glare and no glare contrast sensitivity were improved at 3cd, 12cd and 18cd, with the exception of 6cd. The aberration decreased in RMS, spherical and coma. Post operative ACD (1 week after operation) diminished 8.92% as compared with the preoperative ACD. The mean vaulting was (452 ± 216.38) µm (6 months) and ranged 130 - 1080 µm at different follow-up periods. There was no statistically significant difference in vaulting between postoperative data at different periods (t = 0.200, P > 0.05). The mean postoperative ECD decreased but had no statistically difference compared with the preoperative ECD. ACD decreased 31% after surgery in 2 eyes (2.1%). Transient high IOP was observed in 13 eyes (2.1%) one week after the operation. CONCLUSION: These results indicate that ICL implantation in the treatment of myopia is efficient, predictable, safe, and reliable.

[Clinical investigation on anterior capsule preservation in surgical management for severe proliferative diabetic retinopathy].

OBJECTIVE: To report the outcomes of patients treated with the anterior capsule preservation technique used in surgical management for severe proliferative diabetic retinopathy. METHODS: Anterior capsule was preserved following pars plana lensectomy or fragmentation during vitrectomy for cataract patients with proliferative diabetic retinopathy, all eyes presented tractional and tractional/rhegmatogenous retinal detachment and involvement of posterior retina. Postoperatively, the transparency of anterior capsule was classified into A, B, C and D degrees according to the photographic record. The outcomes of visual acuity, retinal reattachment, intraocular pressure and the complications related to the operation as well as their managements were analyzed. RESULTS: Vitrectomy, silicone oil tamponade and anterior capsule preservation were performed in 58 eyes. The transparency of the anterior capsule in these eyes was degree A in 26 eyes (44.8%); degree B in 20 eyes (34.5%); degree C in 7 eyes (12.1%) and degree D in 5 eyes (8.6%). Forty eyes (79.3%) had a postoperative best corrected visual acuity > or = 0.05, 21 eyes received secondary intraocular lens implantation. Finally, 7 eyes were classified to be silicone oil-depended eyes because of severe proliferative changes occurred and the presence of macular hole. Complications related to the operation included iris mal-cut in 1 eye, silicone oil escaped into anterior chamber in 7 eyes, iris neovascularization and new vascular glaucoma in 1 eye respectively, intraocular pressure elevation in 4 eyes, secondary pre-macular membrane formation in 11 eyes and macular hole in 2 eyes. CONCLUSIONS: The anterior capsule preservation procedure and selective secondary intraocular lens implantation is an acceptable method in surgical management for severe proliferative diabetic retinopathy. The main causes of the opacification of anterior capsule are the proliferation of residual lens epithelial cells and blood deposit on the posterior surface. Silicone oil escaped into the anterior chamber is one of the most common complications related to this procedure.

[Regeneration of optic nerve fibers following graded injuries in rats].

OBJECTIVE: To investigate the changes of retinal ganglion cell (RGC) and their axons, and nerve regeneration ability following graded optic nerve injury (ONI) in rats. METHODS: A pair of cross-action forceps with 148.0 g clipping pressure was used to clip rat optic nerves for 3, 6, 12, 30 and 60 s to induce graded ONI animal model. The RGC was counted at 0.5, 1, 2, 3 and 7 months and the axons were observed 1, 2 and 3 months post-injury. The regeneration process was observed by transmission electron microscopy. The number of optic nerve fibers in transverse sections was calculated in silver-stained longitudinal sections, and a regeneration index (RI) was calculated based on these numbers. The RI, reflecting the regeneration ability of injured optic nerves, was calculated as follows: (number of nerve fibers 0.5 mm behind injury site-number of nerve fibers 2.5 mm behind injury site)/(number of nerve fibers 0.5 mm retrobulbarly-number of nerve fibers 2.5 mm behind injury site). RESULTS: RGC and axons lost continuously after partial ONI. The loss of RGC was fitted with exponential pattern consisted of two phases, acute losing phase within first two weeks post injury and followed by another phase characterized by slowly reducing of RGC. The loss ratio of RGC increased and the survival ratio decreased with the severity of injury intensity. The loss of RGC and axons was aggregated in severe injury and showed a self-limited trend in mild injury. A large amount of clustered, zonal unmyelinated regeneration fibers were present after injury. The RI was 1.409, 1.490, 0.916, 1.119 and 1.224 following 3, 6, 12, 30 and 60 s clipping injury (chi2 = 281.2, P < 0.01), respectively. Different RI was associated to different injury intensity, with a greater regeneration ability in mild injury. CONCLUSIONS: The secondary reaction and regeneration ability vary with graded intensity of optic nerve injury. A self-limited secondary reaction and a more powerful regeneration ability are associated with a mild injury. The repair behavior and the injury may reach a balance and result in a successful regeneration after a certain degree of injury.