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Background: There are ON- and OFF-pathways in the normal vertebrate retina. Short- and long-flash electroretinogram (ERG) are suitable methods to observe the function of ON- and OFF-pathways in vivo, respectively. It is clear that high intraocular pressure (IOP) might cause dysfunction of cone-dominated photopic negative response (PhNR) in monkeys with high IOP in ON-pathway. However, whether cone-dominated OFF-responses are also affected is less known. The aim of this study was to observe photopic OFF-responses of ERG in monkeys with high IOP. Methods: Nine monkeys were involved in the experiment from January 2006 to December 2016. High IOP was induced in the right eye by laser coagulation of the mid-trabecular meshwork in five monkeys. Six years after the laser coagulation, both short- and long-flash of the photopic ERG were recorded. Stimulus light was red flashes superimposed on a blue background. Four normal monkeys were examined under the same ERG protocols as controls. Paired t-test was used to compare the difference of each ERG parameter between the lasered eye and the fellow eye. Analysis of variance (ANOVA) with Tukey adjustment was adopted to calculate the differences among the lasered eye, the fellow eye, and the eyes of normal monkeys. Results: The mean amplitude of a-wave (11.73 ± 2.05) and PhNR (8.67 ± 2.44) in lasered eyes was significantly lower than that of a-wave (21.47 ± 3.15) and PhNR (22.05 ± 3.42) in fellow eyes (P = 0.03 and P = 0.01, respectively) in response to short flash. The mean amplitude of d-wave (1.60 ± 0.59) and i-wave (3.13 ± 0.64) was significantly reduced in the lasered eyes than that of d-wave (4.01 ± 0.56) and i-wave (8.79 ± 1.75) in the fellow eyes (P = 0.02 and P = 0.02, respectively) in response to long flash. Conclusions: Reduced OFF-responses are recorded in monkeys with high IOP when dysfunction of photoreceptor is involved. The reduced OFF-responses to long-flash stimulus show evidence of anomalous retinal circuitry in glaucomatous retinopathy. Key words: Electroretinogram; OFF-responses; Monkey; Intraocular Pressure; Retinal Pathway

Background: A sensitive method is required to detect retinal hamartomas in patients with tuberous sclerosis complex (TSC). The aim of the present study was to compare the color fundus photography, infrared imaging (IFG), and optical coherence tomography (OCT) in the detection rate of retinal hamartoma in patients with TSC. Methods: This study included 11 patients (22 eyes) with TSC, who underwent color fundus photography, IFG, and spectral-domain OCT to detect retinal hamartomas. TSC1 and TSC2 mutations were tested in eight patients. Results: The mean age of the 11 patients was 8.0 ± 2.1 years. The mean spherical equivalent was −0.55 ± 1.42 D by autorefraction with cycloplegia. In 11 patients (22 eyes), OCT, infrared fundus photography, and color fundus photography revealed 26, 18, and 9 hamartomas, respectively. The predominant hamartoma was type I (55.6%). All the hamartomas that detected by color fundus photography or IFG can be detected by OCT. Conclusion: Among the methods of color fundus photography, IFG, and OCT, the OCT has higher detection rate for retinal hamartoma in TSC patients; therefore, OCT might be promising for the clinical diagnosis of TSC.

Background: Though trabeculectomy is often performed on patients with medically refractive pigmentary glaucoma (PG), the clinical outcomes of surgical treatment on PG remain unknown. The aim of this study was to summarize the long-term efficacy and safety of trabeculectomy on PG. Methods: This was a prospective case series observational study. Eighteen consecutive PG patients were followed up for 8 years after trabeculectomy from May 2006 to April 2007. Visual acuity (VA), best-corrected visual acuity (BCVA), slit lamp biomicroscopy, intraocular pressure (IOP) measurement, Humphrey visual field analysis (VFA), and stereoscopic funduscopy were performed on admission and every 6 months after the surgery. Postoperative IOP, VA, BCVA, VFA, adjunctive anti-glaucoma medication, treatment-related side-effects, changes in blebs, and main clinical findings in the anterior segment of PG were recorded and compared with the baseline. Results: Eighteen PG eyes from 18 patients, with average preoperative IOP of 34.5 ± 4.7 mmHg (range: 21–47 mmHg, 1 mmHg=0.133 kPa) were enrolled in this study. All enrolled patients completed the follow-up visits and required examinations. Eight years after trabeculectomy, all surgical eyes (18/18) had satisfactory IOP control with an average of 13.7 ± 2.5 mmHg (range: 9–19 mmHg), which was significantly lower than baseline ( P = 0.001). Majority (15/18) of the PG eyes had stable VA, BCVA, VFA, and optic disc cupping parameters. Functional blebs still existed in 12/18 of the PG eyes at the last follow-up visit. Unanimously, pigmentation in the anterior segment attenuated with time after surgical treatment. No severe side-effects were recorded in any of the surgical eyes. Conclusions: All surgical PG eyes in this study had satisfactory IOP control 8 years after the surgery with well-preserved visual function. The long-term efficacy and safety of trabeculectomy are promising in PG patients.

Background: Optical coherence tomography (OCT) angiography is a novel technique by which we can detect the local perfusion of fundus directly. The aim of this study was to evaluate the reproducibility of optic disc and macular flow perfusion parameters in rhesus monkeys using OCT angiography. Methods: Eighteen healthy monkeys (18 eyes) were subjected to optic disc and macula flow index measurements via a high-speed and high-resolution spectral-domain OCT XR Avanti with a split-spectrum amplitude de-correlation angiography algorithm. Right eye was imaged 3 times during the first examination and once during each of the two following examinations. The intra-visit and inter-visit intraclass correlation coefficients (ICCs) were both determined. Results: The average flow indices of the four optic disc area layers were 0.171 ± 0.009 (optic nerve head), 0.015 ± 0.004 (vitreous), 0.052 ± 0.009 (radial peripapillary capillary), and 0.167 ± 0.011 (choroid). Average flow indices of the four macula area layers were 0.044 ± 0.011 (superficial retina), 0.036 ± 0.011 (deep retina), 0.016 ± 0.009 (outer retina), and 0.155 ± 0.013 (choroid). Intra-visit (ICC value: 0.821–0.954) and inter-visit (ICC value: 0.844–0.899) repeatability were both high. Conclusions: The study is about the reproducibility of optic disc and macular perfusion parameters as measured by OCT angiography in healthy rhesus monkeys. Flow index measurement reproducibility is high for both the optic disc and macula of normal monkey eyes. OCT angiography might be a useful technique to assess changes when examining monkeys with experimental ocular diseases.

Background Glaucoma can cause progressive damage to retinal ganglion cells. These cells can be classified as cells projecting to the superior colliculus and melanopsin-containing retinal ganglion cells, which project to the suprachiasmatic nucleus. This study was to investigate the effects of chronic intraocular pressure elevation on melanopsin-containing retinal ganglion cells in rats. Methods Chronic intraocular pressure elevation was induced in one eye of adult Wistar rats by cauterization of three episcleral veins. Intraocular pressure was measured at different intervals with a rebound tonometer. Superior collicular retinal ganglion cells were retrogradely labeled from the superior colliculus with Fluorogold. Melanopsin-containing retinal ganglion cells were visualized by free-floating immunohistochemistry on whole-mount retinas. The number of labeled superior collicular and melanopsin-containing retinal ganglion cells were counted in the sample areas on flat-mounted retinas. Results Compared with contralateral control eyes, the numbers of both superior collicular and melanopsin-containing retinal ganglion cells were significantly reduced after 12 weeks of experimental intraocular pressure elevation ((2317.41 +/- 29.96)/mm(2) vs (1815.82 +/- 24.25)/mm(2); (26.20 +/- 2.10)/mm(2) vs (20.62 +/- 1.52)/mm(2), respectively). The extent of cell loss of the two types of retinal ganglion cells was similar. However, no morphologic changes were found in melanopsin-containing retinal ganglion cells. Conclusion Both melanopsin-containing and superior collicular retinal ganglion cells were damaged by chronic ocular hypertension, indicating that glaucomatous neural degeneration involves the non-image-forming visual pathway.

BACKGROUND Laser in situ keratomileusis (LASIK) has become an efficient and commonly performed procedure to reduce refractive errors. In order to further increase the postoperative visual quality, the wavefront-guided refractive surgery has been a research hotspot in customized surgery. This study was conducted to compare the visual acuity, higher-order aberration, and contrast sensitivity of wavefront-guided LASIK with iris-registration and conventional LASIK. METHODS Two hundred and eleven myopic eyes of 109 patients were enrolled in this prospective study and randomly divided into two groups: the wavefront-guided LASIK (wg LASIK) group (94 eyes) and conventional LASIK group (117 eyes). A Wavescan Wavefront aberrometer was used to analyze Zernike coefficients and the root-mean-square (RMS) of higher order aberrations with 6.0 mm pupil size, and Optec 6500 visual function instrument was used to measure contrast sensitivity (CS) under 5 spatial frequencies before and after surgery in both groups. RESULTS The uncorrected visual acuity (UCVA) and the mean spherical equivalent (SE) in wg LASIK group were significantly better than those in conventional LASIK (UCVA, z = 2.339, P = 0.019; SE, t = 2.838, P = 0.005) at 3 months after surgery. Moreover, the increase in Z(3)(-3), Z(3)(1), Z(3)(3), Z(4)(0), Z(5)(-1), Z(5)(1), Z(5)(5) and Z(6)(-6) in wg LASIK group was statistically smaller than that in conventional LASIK group (P < 0.05). In wg LASIK group, eyes with a higher amount of the preoperative RMS of the higher order aberrations (RMSh = 0.30 microm) showed a statistically lower increase (13.5%) than those in conventional LASIK group at 3 months after surgery (33.3%) (P = 0.004). And the values of 4th order spherical aberration (4thSA) and the root mean square of 6th order aberration (RMS6) in wg LASIK group were significantly lower than those in conventional group in eyes which had higher preoperative astigmatism (= 1.0D) (4thSA, P = 0.03; RMS6, P = 0.02). Wg LASIK group showed better CS values than the correspondingly preoperative values at all spatial frequencies with and without glare at 3 months after the surgery while conventional LASIK group displayed reduced CS values except for 1.5 and 3 cycles per degree with glare. The differences between the two groups were statistically significant (P < 0.001). CONCLUSIONS Wavefront-guided LASIK with iris-registration is efficient to reduce higher order aberrations especially spherical and coma aberrations, and to improve postoperative visual acuity and contrast sensitivity compared with conventional LASIK. The application of wavefront-guided LASIK with iris-registration is particularly suitable for eyes with higher preoperative RMSh values and eyes with higher preoperative astigmatism.

The evaluation of retinal image quality in cataract eyes has gained importance and the clinical modulation transfer functions (MTF) can obtained by aberrometer and double pass (DP) system. This study aimed to compare MTF derived from a ray tracing aberrometer and a DP system in early cataractous and normal eyes.There were 128 subjects with 61 control eyes and 67 eyes with early cataract defined according to the Lens Opacities Classification System III. A laser ray-tracing wavefront aberrometer (iTrace) and a double pass (DP) system (OQAS) assessed ocular MTF for 6.0 mm pupil diameters following dilation. Areas under the MTF (AUMTF) and their correlations were analyzed. Stepwise multiple regression analysis assessed factors affecting the differences between iTrace- and OQAS-derived AUMTF for the early cataract group.For both early cataract and control groups, iTrace-derived MTFs were higher than OQAS-derived MTFs across a range of spatial frequencies (P0.01). No significant difference between the two groups occurred for iTrace-derived AUMTF, but the early cataract group had significantly smaller OQAS-derived AUMTF than did the control group (P0.01). AUMTF determined from both the techniques demonstrated significant correlations with nuclear opacities, higher-order aberrations (HOAs), visual acuity, and contrast sensitivity functions, while the OQAS-derived AUMTF also demonstrated significant correlations with age and cortical opacity grade. The factors significantly affecting the difference between iTrace and OQAS AUMTF were root-mean-squared HOAs (standardized beta coefficient = -0.63, P0.01) and age (standardized beta coefficient = 0.26, P0.01).MTFs determined from a iTrace and a DP system (OQAS) differ significantly in early cataractous and normal subjects. Correlations with visual performance were higher for the DP system. OQAS-derived MTF may be useful as an indicator of visual performance in early cataract eyes.

Assessment of the optic disc and retinal nerve fiber layer (RNFL) is essential for the diagnosis and monitoring of glaucoma. Knowledge of normal optic disc topography provides a benchmark for evaluating glaucomatous pathologic changes, especially in its early stages. The purpose of this study was to evaluate the characteristics and correlation factors of the optic disc parameters using the Heidelberg Retina Tomograph II (HRT II) in a large sample of normal eyes of adult Chinese subjects.Disc data were obtained from 6 830 subjects aged30 years from the Handan Eye Study. All participants underwent comprehensive eye examinations and physical examinations. The associations of gender, age, body mass index, blood pressure, waist-to-hip ratio; refractive error, intraocular pressure, axial length, and disc area were assessed using simple and multiple regression analysis. The correlation between HRT II parameters was evaluated.Of the 7 557 eligible subjects, 6 830 took part in the study (90.4% response rate) and 2 633 normal eyes with good-quality HRT II images were selected. The mean disc area was 2.28 mm(2) (standard deviation (SD) 0.43) and mean neural rim area was 1.80 mm(2) (SD 0.29). In multiple regression analysis, optic disc area significantly correlated with age, gender, and axial length (P0.001). All optic disc parameters showed a significant correlation with disc area (0.054r0.736, P0.01). The association between mean RNFL thickness and rim area is statistically significant but not strong (regression linear equation: rim area = 1.42 × mean RNFL thickness + 1.32 mm(2), P0.001; R(2) = 0.070). The global RNFL cross-sectional area was significantly associated with global rim area (regression linear equation: rim area = 1.14 × RNFL cross-sectional area + 0.44 mm(2), P0.001; R(2) = 0.271).The optic disc area in rural Chinese population is larger than reported in white and Japanese populations, similar to that of Indian population and urban Chinese population. Most optic disc measurements were moderately or weakly affected by disc area. In addition to the RNFL, there may be other factors affecting the rim area. The relationship between optic disc and axial length may suggest a link between larger disc area, thinning of the lamina cribrosa, and increased glaucoma susceptibility in myopic eyes.

BACKGROUND Latanoprost, a prostaglandin F2alpha analog, has been shown to be an effective intraocular pressure lowering agent which acts by inducing ciliary muscle cells to synthesise matrix metalloproteinases. However, the response of ciliary melanocytes to latanoprost has never been reported. This research has investigated the ability of latanoprost to induce matrix metalloproteinase-1 expression in human ciliary melanocytes, and thereby advance the understanding of the mechanism of PGF(2alpha) in decreasing intraocular pressure. METHODS In vitro human ciliary melanocytes were treated for 48 hours with five different concentrations of latanoprost (100, 150, 200, 500, and 1000 nmol/L). Ciliary melanocytes treated with 0.01% ethanol (vehicle) were used as a control. The expression of matrix metalloproteinase-1 in ciliary melanocytes was determined by Western blotting and immunofluorescent staining. RESULTS Western blotting showed that the expression of matrix metalloproteinase-1 in ciliary melanocytes was induced by latanoprost, and the level of expression was dependent on the concentration of latanoprost in the culture medium. Immunofluorescent staining showed that matrix metalloproteinase-1 was confined to the ciliary melanocyte cytoplasm. CONCLUSIONS Latanoprost induced the expression of matrix metalloproteinase-1 in human ciliary melanocytes in a dose-dependent manner. Ciliary melanocytes, as well as ciliary muscle cells, may also play an important role in uveoscleral outflow modulation.

Background Congenital cataract is a highly heterogeneous disorder at both the genetic and phenotypic levels. This study was conducted to identify disease locus for autosomal dominant congenital cataracts in a four generation Chinese family. Methods Family history and clinical data were recorded. All the members were genotyped with microsatellite markers which are close to the known genetic loci for autosomal congenital cataracts. Two-point Lod scores were obtained using the MLINK of the LINKAGE program package (ver 5.1). Candidate genes were amplified by polymerase chain reaction (PCR) and direct cycle sequencing. Results The maximum Lod score of Zmax=2.11 was obtained with three microsatellite markers D22S258, D22S315, and D22S1163 at recombination fraction theta= 0. Haplotype analysis showed that the disease gene was localized to a 18.5 Mbp region on chromosome 22 flanked by markers D22S1174 and D22S270, spanning the P-crystallin gene cluster. A c.752T -> C mutation in exon 6 of CRYBB1 gene, which resulted in a heterozygous S228P mutation in predicted protein, was found to cosegregate with cataract in the family. Conclusions This study identified a novel mutation in CRYBB1 gene in a Chinese family with autosomal dominant congenital cataract. These results provide strong evidence that CRYBB1 is a pathogenic gene for congenital cataract.

To review the major progress in primary angle closure glaucoma (PACG).Contents of this article were selected from the original papers or reviews related to primary angle closure glaucoma published in Chinese and foreign journals. A total of 76 articles were selected from several hundred original articles or reviews. The content of selected articles is in accordance with our purpose and the authors are authorized scientists in the study of glaucoma.Primary angle closure glaucoma is the most common type of glaucoma in the Sino-Mongoloid population. PACG in Chinese can be classified into three types depending on the mechanism of angle closure: 1. Multimechanism: 54.8% of Chinese PACG is caused by co-existing factors. The pattern of angle closure appears to mainly be creeping closure. After iridectomy, almost 40% of the cases still manifest a positive response to the darkroom provocative test and progressive synechial closure or recurrent angle closure may occur. Several mechanisms are involved in this form of PACG such as pupillary blocking component, iris crowding component and anterior positioned ciliary body. These factors can coexist in the follow patterns: pupillary blocking and iris crowding coexist; pupillary blocking and anterior positioned ciliary body coexist or three of them co-exist. 2. Pupillary block: (38.1% of Chinese PACG) is caused by iris bombe due to pupillary block with acute or subacute attack. It responds well to iridectomy or laser iridotomy. 3. Non-pupillary blocking: (7.8% of Chinese PACG). They usually have a deeper anterior chamber, and tend to be younger (below 40 years of age). Angle closure in this form of PACG is caused by: iris crowding mechanism or/and anteriorly positioned ciliary body against iris root to angle. It is critical to distinguish multi-mechanism PACG from other types. The initial treatment for this type of PACG is also iridectomy, but after the pupillary block component is eliminated by iridectomy, the residual non-pupillary blocking components should be highlighted by a diagnostic treatment procedure or by a ultrasound biomicroscopy (UBM) provocative test. Finally, the role of UBM in the observation and evaluation of the mechanism of angle closure is discussed and future research directions on PACG in Asians are proposed.Chinese eyes have been recognized to be prone to the development of creeping angle closure. There is some direct evidence that creeping angle closure is caused by multiple mechanisms. Further study on this topic is needed.

To investigate in vivo survival of retinal ganglion cells (RGCs) after partial blockage of optic nerve (ON) axoplasmic flow by sub-retinal space or vitreous cavity injection of brain-derived neural factor (BDNF) produced by genetically modified neural progenitor cells (NPCs).Adult Sprague-Dawley (SD) rat RGCs were labeled with granular blue (GB) applied to their main targets in the brain. Seven days later, the left ON was intra-obitally crushed with a 40 g power forceps to partially block ON axoplasmic flow. Animals were randomized to three groups. The left eye of each rat received a sham injection, NPCs injection or an injection of genetically modified neural progenitors producing BDNF (BDNF-NPCs). Seven, 15 and 30 days after ON crush, retinas were examined under a fluorescence microscope. By calculating and comparing the average RGCs densities and RGC apoptosis density, RGC survival was estimated and the neuro-protective effect of transplanted cells was evaluated.Seven, 15 and 30 days after crush, in the intra-vitreous injection group, mean RGC densities had decreased to 1885 +/- 68, 1562 +/- 20, 1380 +/- 7 and 1837 +/- 46, 1561 +/- 58, 1370 +/- 16, respectively with sham injection or neural progenitors injection. However, RGCs density in the groups treated with intra-vitreous injection of BDNF-NPC was 2101 +/- 15, 1809 +/- 19 and 1625 +/- 34. Similar results were found in groups after sub-retinal injection. Higher densities were observed in groups treated with BDNF-NPCs. There were statistically significant differences among groups through nonparametric tests followed by the Mann-Whitely test. RGC apoptosis density in BDNF-NPC at each follow-up time was less than in other groups.A continuous supply of neurotrophic factors by the injection of genetically modified neural progenitors presents a highly effective approach to counteract optic neuropathy and RGC degeneration after partial ON axoplasmic flow blockage.