Volume 51 · Issue 05 · 2015

Retina is the classic"neurovascular coupling" tissue, and coordinate the bioactivity of neurobiology and retinal blood flow. Müller glia cells span the entire thickness of the tissue, and ensheath all retinal neurons and microvascular of the retina. This morphological relationship is reflected by a multitude of functional interactions between neurons and blood-retinal barrier, and play fundamental roles in diabetic retinopathy. However, in recent studies, the mechanisms of Müller glia cells in retinal neurodegeneration and microcirculatory abnormalities of diabetic retinopathy are underestimating. Therefore, the present article reaffirms the interrelationship between Müller glia cells and diabetic retinopathy to draw the attentions of researchers. (Chin J Ophthalmol, 2015, 51:321-322)

ischemic optic neuropathy (ION) is a group of common optic nerve diseases that seriously harm visual function, including many types, each with its own etiology, pathogenesis, clinical manifestations and treatment methods. At present, there are still many differences in the pathogenesis and clinical manifestations of various types of diseases, especially the treatment methods. Non-arteritic anterior ischemic optic neuropathy is the most common type, the incidence rate can reach 0.23/10,000~1.02/10,000, and can occur at any age, and 89% of them are over 45 years old. It is one of the important causes of harming the visual function of middle-aged and elderly people^[1]。

World Health Organization (WHO) trachoma rapid assessment (TRA)^[1]It is a simple, fast and low-cost examination method for collecting the latest and most relevant information and data of trachoma. This evaluation method can make full use of the limited resources in the surveyed area for data collection, clarify whether trachoma is prevalent in the area, whether blinding trachoma is a public health problem, etc., understand the existing risk factors of trachoma, and determine the priority and distribution of interventions, and decide whether to implement cost-effective large-scale interventions to eradicate blinding trachoma, i.e. SAFE strategy [trachomatous trichiasis (TT) correction surgery (S), use of appropriate antibiotic treatment (A), face washing (F), environmental improvements (E)]^[2]。

The visual acuity of the retina is divided into central vision and peripheral vision. The central vision is the vision at the time of fixation, and the peripheral vision is the field of vision. The fovea occupies the advantage of congenital tissue structure, and its corresponding central vision is stable in fixation, and the ability of image analysis is strong. Compared with central visual acuity, peripheral visual acuity is sharply reduced, fixation is unstable, and the ability of image resolution is decreased. When the two visual acuities coexist in the physiological state, the visual acuity detected by the ordinary eye chart (gazing at characters) is the central visual acuity of the fovea, and the periretinal visual acuity cannot be checked. The central absolute dark spot appears on the visual field of the affected eye (here refers to all kinds of absolute dark spots involving the fovea in addition to the typical central absolute dark spot). When the central vision is lost, the retina appears eccentric fixation. At this time, the author thinks that the vision chart visual acuity^[1,2,3]For peripheral vision^[4,5,6]。 Therefore, the visual acuity of the affected eye seen in clinic is not only central vision, but also peripheral vision. The two kinds of vision come from different parts of the retina, and the functions of perception of vision in different parts of the retina are different, and there are qualitative differences. Therefore, it is necessary to analyze the visual properties of eye diseases with absolute central dark spots (such as optic neuropathy, macular fovea disease, etc.) in clinic, to determine whether it is central vision or peripheral vision, and make reasonable diagnosis and treatment according to the visual properties. This is for the author to put forward the theory of visual properties analysis based on the two kinds of visual views. The nature of visual acuity should be determined according to the presence or absence of absolute dark spots in the fovea of the affected eye^[7]。 The main differences between the eyes affected by the two visual properties areTable 1。

Visual acuity is an important component of visual function, and visual acuity examination is the most basic and commonly used examination method in ophthalmology. The results of visual acuity examination are usually used as an index to reflect visual function and judge the changes of disease. The author has some different views on the understanding of visual acuity, especially the relationship and interpretation of visual impairment and visual function in clinical practice and clinical research in the article "Exploring the Method of Correct Statistical Vision Data and True and False Paracentric Dark Spots" published in this issue, which is put forward here and discussed with the author.

In visual field detection, to accurately detect the sensitivity of each position of the retina, it is necessary to clarify the position of each visual target projected to the retina. The position of the visual target on the stimulation screen is determined during the detection process, and the position of the visual target projected on the retina is affected by the gaze direction of the examined eye at the moment when the visual target appears^[1]。 At the moment when the visual target is presented, when the subject's head is upright, the eye is directly looking forward, and the visual axis is pointed at the fixation target, the retinal stimulated site is consistent with the site set by the detection program. If the target is presented at an incorrect fixation position, the target is projected at a position on the retina that is not expected to be set by the detection program. Due to the different sensitivity of retina to light stimulation in different regions, the physiological difference of retinal sensitivity between the actual stimulated site and the expected set site may lead to abnormal visual field detection results in the examined eye with completely normal visual field; However, this difference may be more significant for the examined eyes with abnormal visual field, resulting in deviations in the defect area and depth of the abnormal visual field^[2]。 Therefore, the wrong gaze direction of the inspected eye will affect the reliability of the visual field detection results, and the correct gaze direction is the prerequisite to ensure the accuracy of the visual field detection results.

To investigate the association between the variable number of tandem repeats (VNTR) polymorphism 4a/b in the endothelial nitric oxide synthase (eNOS) gene and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus.

cross-sectional study. A total of 278 type 2 diabetes patients were recruited, of whom 130 had DR, and 148 had diabetes without retinopathy (DWR). Of the 130 patients with DR, 34 had proliferative DR (PDR) and 96 had non-proliferative DR (NPDR). A number of 223 volunteers without diabetes from the same area were recruited as the control group. PCR and agarose gel electrophoresis methods were adopted to determine the 4a/b polymorphism genotypes of the eNOS gene. Statistical analysis was performed using the R statistical analysis package. Genotype distribution was compared using the χ ² test. Numerical data were examined by Student t test. Genotypes and allele frequencies between cases and controls were compared using the χ ² test or Fisher's exact test. Odd ratios (OR) and 95% confidence intervals (CI) were calculated according to the Woolf's equation.

The frequencies of minor alleles (a) were 10.8% and 11.5% in the DR and DWR group, respectively. There were no statistical differences between the two groups (χ²=0.07,P=0.789). Also there were no statistical differences (χ²=0.88;P=0.643) in the distributions of the genotypes between DR group (bb 78.5%, ab 21.5%, aa 0.0%) and DWR group(bb 77.7%, ab 21.6%, aa 0.7%). Statistical differences were found in the frequencies of alleles, and the distributions of genotypes between diabetes group and the control group (χ²=8.75, 10.39,P=0.003, 0.006). However, after adjustment for age, blood pressure, cholesterol concentration, blood-fat and so on, it became insignificant(χ²=0.97, 1.25,P=3.224, 0.812). In the multiple regressions model including clinic factors such as the age of onset of diabetes, urinary albumin, insulin using, creatinine, glycated hemoglobin and fast glucose, no evidence showed that eNOS gene VNTR 4a/b was associated with diabetic retinopathy (OR=0.37, 95%CI: 0.15- 0.95).

There was no significant association between eNOS gene VNTR 4a/b polymorphism and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus. (Chin J Ophthalmol, 2015, 51:338-343)

To formulate and evaluate polymeric liposomes(PL) nanoparticles as a novel non-viral gene delivery. To explore its applicability and feasibility as a non-viral vector for gene transportation.

Experimental study. To construct the orongoxygen induced retinopathy(OIR)mouse (C57BL/6J) model on the basis of improved Smith's methods. Western blot was used to measure VEGF protein expression in retinal tissue at P17 and P22. HE staining and fluorescein-dextran angiography of retinal vascular were performed to observe the morphologic alterations of retinal neovascularization. Frozen-section was used to show the membrane translocation of PL.

In fluorescence angiograms, irregular neovascularization and fluoresce leakage were observed in OIR model. The results of Western blot showed that VEGF protein in retinal tissues were significantly different among groups(F=158.207,P=0.000) at P17 and P22(F=25.695,P=0.000). The protein level was lower in both PL(0.70±0.03) and Lipo group (0.66±0.04) at P17 (P=0.092), and the lower level was presented at P22 in PL group (0.50±0.03) than in Lipo group(0.53±0.05) (P<0.05). HE staining were performed to observe the significantly improvements of retinal neovascularization in PL(28.0±3.44) and Lipo group(24.50±3.06) at P17. Moreover, inhibitory effects maintained at P22 in PL group (11.70±3.09) as HE staining showed. Fluorescein angiography of retinal vascular showed retinal non-perfusion and neovascularization areas were smaller in both PL and Lipo group at P17. Frozen-section examination showed the property of membrane translocation. GFP expression could be seen in vitreous cavity just at first day post-intravitreal administration in PL and Lipo group, which could reach their peaks in external retina nearby RPE layer at P17, remaining at P22 in PL group.

The PL performed excellent ability of membrane translocation and it was a kind of slow steady released gene vector.(Chin J Ophthalmol, 2015, 51:344-350)

To investigate the mediation of HIF-1α siRNA to the leukocyte adhesion and myeloid cell's activity in rat's retina at early stage of diabetic retinopathy.

Experimental study. HIF-1α specific siRNA expression vector pSUPERH1-siHIF1α was constructed by gene recombination. The rat diabetic model was induced by intraperitoneal injection of streptozotocin. After 2 months of diabetes induction, 27 diabetic rats were randomly chosen and assigned to 3 groups, including diabetes and phosphate buffered saline (PBS) vitreous injection group (group B), diabetes and pSUPERH1-siHIF1α vitreous transfect group (group C) and diabetes and pSUPER-retro vitreous transfect group (group D). Each group had 9 rats. Nine age matched health rats were chosen as control group (group A). Retinal leukostasis was quantified with acridine orange leukocyte fluorography. Retinal myeloid cell activity was measured by enzyme linked immunosorbent assay of myeloperoxidase(MPO). The differences of the mean values among the four groups were analyzed by one-factor analysis of variance. The multiple comparisons of the mean values among the four groups were analyzed by LSD-t analysis.

According to the results of the acridine orange leukocyte fluorography, the numbers of leukocyte adhesion in the four groups were (47.00±3.60), (155.33±9.01), (76.00±9.05), (142.66±10.26), respectively. The differences among them were significant (F=116.25,P=0.00). The number of leukocyte adhesion in the group C was significantly lower than that in group B(LSD-t test,P=0.00, 95%CI: 3.56–95.10). The levels of retinal MPO in the four groups were (17.24±1.13), (31.32±2.53), (21.35±1.06), (31.33±1.26) μg/L, respectively. The differences among them were significant( F=58.68,P=0.00). The level of retinal MPO in the group C was significantly lower than that in group B(LSD-t test,P=0.00, 95%CI: 6.92–13.01).

HIF-1α siRNA may play a role in the mediation of the leukocyte adhesion and myeloid cell's activity in rat's retina at early stage of diabetic retinopathyin vivo.(Chin J Ophthalmol, 2015, 51:351-355)

To investigate whether ranibizumab can penetrate into the retina after subconjunctival injection in a rabbit model.

Experimental study. Fifty-six New Zealand rabbits were randomly divided into four groups: control group (3), saline subconjunctival injection group (3), ranibizumab intravitreal injection group (25) and ranibizumab subconjunctival injection group (25). Each rabbit received single injection in right eye. Ranibizumab's location and concentrations in the retina and aqueous humor were determined by immunofluorescence staining and ELISA at 1, 2, 4, 8, 12 weeks after injection. The comparison of ranibizumab concentration data was analyzed byt-test.

The concentrations of aqueous humor in intravitreal injection group, determined by ELISA, were (389.67±22.55), (319.33±17.93), (22.67±3.06), (9.67±1.53) and (7.33±2.18) mg/L at 1, 2, 4, 8, 12 weeks respectively. Concentrations of subconjunctival injection group were (53.67±3.21), (12.67±3.06), (8.33±1.53), (2.66±2.08) mg/L at 1,2,4,8 weeks and had a statistical difference compared with intravitreal injection group at each time point( t=32.96, 38.39, 7.67, 11.07,P<0.05). But there was no detection at 12 weeks. Similar in retina immunofluorescence staining results, the ranibizumab positive signals were detected in all the time points except the last one in subconjunctival injection group.

Subconjunctival ranibizumab injection may be able to penetrate into retina. (Chin J Ophthalmol, 2015, 51:356-359)

The purpose of the current research was to investigate the NDP (Norrie disease protein) gene in one Chinese family with Norrie disease (ND) and to characterize the related clinical features.

Clinical data of the proband and his family members were collected. Complete ophthalmic examinations were carried out on the proband. Genomic DNA was extracted from peripheral blood leukocytes of 35 family members. Molecular analysis of the NDP gene was performed by polymerase chain reaction and direct sequencing of all exons and flanking regions.

A hemizygous NDP missense mutation c.362G> A (p. Arg121Gln) in exon 3 was identified in the affected members, but not in any of the unaffected family individuals.

The missense mutation c.362G> A in NDP is responsible for the Norrie disease in this family. This discovery will help provide the family members with accurate and reliable genetic counseling and prenatal diagnosis.(Chin J Ophthalmol, 2015, 51:360-363)

Analysis ophthalmic manifestations in acquired immune deficiency syndrome(AIDS) patients with cryptococcal meningitis.

Retrospective study. Forty AIDS patients (including 32 men and 8 women) with cryptococcal meningitis were studied. The age of the patients varied from 11 to 67 years, average on (38±12) years (mean±standard deviation). All the patients underwent detailed ocular examinations including corrected visual acuity, eye movement, intraocular pressure, slit lamp microscope, indirect ophthalmoscope and color fundus photography. The CD₄⁺ T cell count was evaluated and Lumbar puncture was done to examine the cerebral spinal fluid(CSF). Eighteen patients were followed up for a period between 2weeks to 4years. Four patients died during hospitalization. The remaining 18 patients failed to be followed up due to moving away.

Binocular diplopia were present in 3 patients. It showed Binocular or monocular abducens nerve palsy. Papilledema were found in 37 eyes of 19 cases. One person had unilateral papilledema. Among 19 cases, 24 eyes of 12 cases were accompanied with peripapillary hemorrhages and 7 cases of 13 eyes without peripapillary hemorrhages. Optic atrophy occurs in 6 cases of 12 eyes and multifocal choroiditis in 2 cases of 4 eyes. Twenty-seven eyes of 14 patients had normal fundus or cytomegalovirus retinitis(CMVR) only.

AIDS patients with cryptococcal meningitis merger may be accompanied by a variety of eye complications. Papilledema are the most common manifestations. (Chin J Ophthalmol, 2015, 51:364-368)

To investigate the contributions of human rods and cones pathway to different components of oscillatory potentials (OP) in time and frequency domain.

Case-control study. Twenty subjects were divided into two groups, normal groups (NG) and cones pathway abnormal groups (CAG). All eyes were investigated by dark-adapted (DA) and light-adapted (LA) 3.0 ERG recommended by ISCEV. Data were output into the computer and processed and analyzed by the software Matlab7.0. First, to extract the OP by filter, then to get the frequency-amplitude relationship by FFT, after that the relationship was fitted by equations and lastly we statistic and analyze the parameters gotten from the equations.

Compared with normal group[(48.63±4.29), (158.00±32.75), (69.27±30.31), (38.5±15.28) μV], the amplitudes of the first two components of dark-adapted OP in the CAG[(4.12±3.20), (71.25±25.43), (48.96±20.05), (36.84±14.26) μV] were significant decreased( t=16.68,5.77,P<0.01). Frequency domain of LA and DA OP in the two groups was comprised with two components (harmonic and subharmonic). Compared with normal group, harmonic components of CAG were dramatic decreased (t=2.72,P<0.05;Z=-2.24,P<0.05). The value of subharmonic component in CAG was lowest in DA OP compared with NG (t=4.20,P<0.005).

Cones and rods pathway all contributed to the DA and LA OP Cones pathway mainly contributes to the earlier and faster components of OP while the rods pathway to the later and slower components. (Chin J Ophthalmol, 2015, 51:369-373)

The patient was a 63-year-old female. On May 18, 2013, I came to Southwest Hospital of the Third Military Medical University for treatment because my vision decreased for half a year after vegetable oil was splashed into my right eye at work. Ophthalmic examination: corrected visual acuity in the right eye was 0.05, and corrected visual acuity in the left eye was 0.8. There was no conjunctiva congestion in the right eye, transparent cornea, retrocorneal deposit (KP) (-), Tyndall's sign (-), slow direct reflection to light, sensitive indirect reflection to light, clear iris texture, transparent lens, clear vitreous body, clear papilla boundary under funduscopy, C/D 0.3, A/V =2/3, flat retina, and a few punctate lesions under the posterior pole. No obvious abnormalities were found in all examinations of the left eye. It was excluded that the loss of vision in the right eye was caused by splashing of vegetable oil. OCT examination revealed the absence of IS/OS layer of photoreceptor cells in part of retinal myopic papilla in the macular area of the right eye, and the reflected signal of RPE layer in this area was reduced (Figure 1A in), suggesting an outer retinal pathology in this area. FFA examination showed that the filling time of the right ophthalmic artery became longer, the boundary of the optic papilla was clear, the shape of macular arch ring existed, a small amount of scattered hyperfluorescence was seen in the macular area and posterior pole, but the fluorescence was not enhanced in the later stage. ICGA examination showed that the border of the binocular papilla was clear, and a small amount of mottled hypofluorescence in the posterior pole fundus was seen in the later stage. Visual field examination revealed that the physiological blind spot of the right eye was enlarged, and the localized visual field defect on the nasal side (Figure 1In B). full field electroretinogram (FERG) dark adaptation 3.0 response of right eye A wave amplitude was severely reduced, and b wave amplitude was mildly to moderately reduced. The amplitude of each wavelet of dark adaptive oscillatory potential decreased severely, the amplitude of A and b waves of clear adaptive 3.0 response decreased severely, and the amplitude of PEAK wave of clear adaptive 30 Hz response decreased severely. multifocal electroretinogram (mfERG) showed that the macular amplitude density in the right eye was decreased, and the myopic papillary area was obvious (Figure 1C in). The abnormal areas of OCT, visual field and mfERG examination had good correspondence. No obvious abnormalities were found in all examinations of the left eye. Clinical diagnosis of acute regional occult outer retinopathy (acute zonal occult outer retinopathy, AZOOR). The patient was given retrobulbar injection of triamcinolone acetonide 20 mg, but the patient did not come to the hospital for examination for some reason. After telephone inquiry, he felt that there was no further significant change in his condition.

Child female, 44 d. On August 23, 2013, he went to the Department of Ophthalmology of Beijing Tongren Hospital affiliated to Capital Medical University because of the discovery of a rash all over his body for 44 days. The child was pregnant 2 and gave birth 2, with a gestational age of 39⁺²gestational age, delivery by cesarean section in other hospital, no abnormal birth history, no amniotic fluid contamination, etc., birth weight of 3300 g, Apgar score of newborns at 1, 5 and 10 minutes were all 10 points, and the history of postnatal oxygen inhalation was denied. After birth, blisters of varying sizes on the skin of the trunk and limbs were found, followed by rupture and scab. There are gray-brown pigment spots on the skin where the scab falls off, which are striped, and some scab spots become brown warty hyperplasia, which is diagnosed as "skin pigment incontinence" in the outside hospital. Her parents are in good health and are not married by close relatives. Her sister has no similar medical history, and has no family history of genetic diseases and skin diseases. Physical examination on admission: The child was in good general condition, moderate nutrition, mature newborn appearance, no teething, and no neurological abnormalities. Brown strip-like pigment deposits can be seen on the skin of the trunk and limbs of the whole body, which are distributed in a splash-like manner, and some blisters and crusts show gray-brown wart-like protrusions (Figure 1）。 Both eyes chase light well, can chase objects, intraocular pressure is normal by finger measurement, conjunctiva is not obviously congested, cornea is transparent, aqueous humor is transparent, iris color is acceptable, pupil is round (about 3 mm in diameter), directly and indirectly sensitive to light reflection, and lens is transparent. Fundus examination with dilated pupils showed that the boundary of the optic papilla in both eyes was clear and reddish in color, the retinal vessels in the posterior pole were tortuous, and the temporal vascular branches increased, forming abnormal anastomotic branches. Right eye from 5: 00-9: 00-1: 00 azimuth peripheral retinal avascular area, no crest-like protuberance (Figure 2), blood vessels can be seen growing into the retina in the peripheral part of the nose. An avascular area was seen in the 360° peripheral retina of the left eye, and a ridge-like bulge of the retina was seen at 4 PD from the optical head on the nasal side from 6: 00 to 11: 00, and blood vessels were seen on the ridge (Figure 3）。

The patient, a 65-year-old female, went to the ophthalmology clinic of the Affiliated Hospital of Guiyang Medical College on October 17, 2013 due to new organisms in both eyes, foreign body sensation, and lacrimal overflow for one month. The patient complained that her skin turned dark one year ago, with obvious underarms, and then the blackening gradually expanded. She had been treated in many places, but the details are unknown. After that, extensive granular new organisms in the oral cavity appeared repeatedly, and pink new organisms in both eyes with lacrimal overflow appeared one month ago. The patient denied a history of diabetes and other diseases, had no history of similar diseases in the family, and had no history of close marriage between his parents. Physical examination: emaciated body type, skin pigmentation in the neck and underarms (Figure 1), the skin of the palm showed velvety changes, local no papules, and dry surface (Figure 2）。 Ophthalmic examination: the visual acuity of both eyes is 0.6, the hyperplasia of papilloma at the conjunctiva of the upper and lower eyelids of both eyes has spread to the upper and lower tears, and the right eye is heavier such as (Figure 3）。 The lens was slightly opaque, and no abnormalities were observed in the fundus. Laboratory tests: Blood lipid and blood glucose concentrations were normal, and blood electrolyte, urine 17-ketone, 17-hydroxyalcohol and aldosterone levels were normal. After multi-department consultation, abdominal CT examination was performed, which revealed gastric adenocarcinoma and was diagnosed as malignant acanthosis nigricans. After total gastrectomy, histopathological examination was performed: low and moderately differentiated adenocarcinoma of gastric body, carcinoma invading the serosa of gastric wall, perigastric lymph nodes and retroperitoneal lymph nodes; Squamous papilloma of the esophagus. After chemotherapy and radiotherapy, a tumor was found in the left lower neck half a year later, and biopsy showed that the lymph node of the left lower neck had metastatic cancer. The patient was informed that the prognosis was poor and the patient abandoned ophthalmic treatment.

The patient, a 50-year-old female, came to Beijing Tongren Eye Center, Beijing Tongren Hospital affiliated to Capital Medical University on September 29, 2013 due to 5-year loss of binocular vision with night blindness, which was aggravated for half a year. Good health in the past, no history of working in snow, high heat environment for a long time or exposure to toxic chemicals. Family history denied. Specialist examination: naked eye visual acuity of right eye 0.03, naked eye visual acuity of left eye 0.02, corrected visual acuity did not improve, non-contact intraocular pressure: right eye 11 mmHg (1 mmHg =0.133 kPa), left eye 10 mmHg. Conjunctiva in both eyes (-), clear cornea, middle-deep anterior chamber, subcorneal deposit (-), aqueous humor flash (-), equal size and round pupils, about 3 mm in diameter, direct and indirect light reflection (+), opacity of binocular cortex, mild opacity of binocular vitreous, no obvious liquefaction and posterior detachment. Fundus examination: the boundary of the papilla in both eyes is clear, the color is pale yellow, the retinal blood vessels are slender, the pigment distribution in the macula is uneven, and there is no obvious pigmentation, crystalline granules and white dot-like granules in the whole fundus (Figure 1)。 flash electroretinogram (fERG) showed that rod response, maximum mixed response, OPs oscillation potential waveforms disappeared in both eyes, single flash cone response, 30 Hz scintillation response amplitude was severely reduced, waveforms nearly disappeared, and the function of the outer to inner layers of the whole retina in both eyes was severely impaired (Figure 2)。 Peripheral visual field examination of both eyes: The yellow visual label examination showed a tubular visual field of 10°, which showed obvious absolute visual field defect, while the red visual label examination only left a visual field less than 5° (Figure 3）。 Color vision examination showed that red, green and blue were all weak in color. Abnormal lipid metabolism. FFA examination showed that the right fundus had uniform mottled transparent fluorescence and masked fluorescence changes, and the retinal blood vessels were slender, partially occluded at the equator; The left fundus showed flaky mottled fluorescence and masked fluorescence changes, thin blood vessels, occlusion in the periphery, and reduced multifocal choroidal filling (Figure 4）。 multifocal electroretinograms (mfERG) showed severe impairment of retinal and macular function at the posterior pole of both eyes (Figure 5）。 OCT examination showed atrophic changes in double macular cone rod cell layer and RPE (Figure 6）。 Clinical diagnosis: Apigmented retinitis pigmentosa in both eyes (retinitis pigmentosa sine pigmento, RPSP).

The patient was a 55-year-old female. In July 2007, he was first diagnosed in Beijing Tongren Eye Center, Beijing Tongren Hospital affiliated to Capital Medical University because of "foreign body sensation in left eye". Ocular examination: the visual acuity of the left eye was 0.8, the intraocular pressure was 14mmHg (1mmHg =0.133kPa), the conjunctiva was not congested, and a slightly raised gray-white nodular mass was seen in the center of the cornea at 9 o'clock, about 2 mm ×2 mm in size, with clear boundaries. Dilated new blood vessels were seen below the nose of the mass, and no obvious abnormalities were found in the anterior chamber, lens and fundus (Figure 1）。 The visual acuity of the right eye was 1.0, the conjunctiva was not congested, the cornea was transparent, and there were no abnormalities in the rest. First diagnosis: corneal epithelial mass of left eye, the cause is to be investigated. Resection of corneal lesions in the left eye under local anesthesia in July 2007. The epithelial mass was closely adhered to the anterior elastic layer of cornea during operation. Postoperatively, "0.5% levofloxacin eye drops and praprofen eye drops" were given 4 times a day to prevent infection. The resected tissues were sent to pathology, and the results showed that the corneal epithelial cells were proliferated, thickened, disordered and active, and the anterior stromal layer fibers were loosely arranged and disordered (only the pathological diagnosis report was kept, and there were no pathological pictures). In November 2008, November 2009, January 2011, November 2011, and November 2013, patients complained of foreign body sensation, red eye, and photophobia in their left eye for five follow-up visits. The examination found that there was gray-white localized bulge in the same part of the left cornea, ranging from 1 to 3 each time. All patients underwent curettage of the left corneal lesion combined with 5% iodine tincture cautery, and performed histopathological examination of the corneal lesion (Figure 2), suggesting atypical hyperplasia of corneal epithelium. Microbiological examination showed no bacterial growth in ordinary culture and negative in fungal culture. At present, 1 year after surgery, the patient was followed up without recurrence. Final diagnosis: atypical hyperplasia of the corneal epithelium in the left eye.

The patient was a 15-year-old male. On February 22, 2012, he came to the Department of Ophthalmology of Xijing Hospital affiliated to the Fourth Military Medical University due to poor visual acuity in his left eye and progressive aggravation for 1 month. The patient had poor visual acuity in his left eye since childhood. He was found to be "refractive error" in a local hospital, but the corrected visual acuity was not improved significantly, so he did not wear glasses for treatment. In February 2011, during a physical examination, it was found that the vision of his left eye was extremely poor, and he was diagnosed as "congenital cataract in his left eye" at a local hospital. The patient was previously in good health and had no history of trauma, radiation exposure, and no family genetic history. Eye examination: visual acuity: 1.0 in right eye and 0.08 in left eye; IOP was 19 mmHg (1 mmHg =0.133 kPa) in the right eye and 12 mmHg in the left eye. When the left eye was examined, the shadow movement was not clear and the corrected visual acuity could not be improved. Bilateral external eyes were normal, and the right eye was normal when observed by slit lamp microscopy; The central cornea of the left eye was thinned, the stroma was slightly opaque, about 4 mm in diameter, and "oil droplet-like" reflection was seen under diffuse light (Figure 1A), the proximal central region of the cornea protrudes forward in a conical shape and becomes significantly thinner under the slit light (Figure 1B), the anterior chamber is deep, the pupil is round, about 3 mm in diameter, and it is sensitive to light reflection. After dilatation, the size and position of the lens are normal, most of the cortex and nucleus are transparent, the curvature of the anterior capsule is normal and transparent, and the posterior subcapsular cortex of the lens is mild discoid opacity under iris irradiation (Figure 1C), the central part of the posterior capsule at the corresponding site is conically bulged to the posterior part under the fissure light (Figure 1D). Funduscopy: The right fundus was normal. After dilatation, the left eye showed mild opacity of the vitreous body. The fundus could not be seen clearly from the central part of the cornea, and the fundus image was seriously distorted from the peripheral part of the lens. The corneal curvature value of the right eye was 43.25/42.5, and that of the left eye was greater than 60. The right side of the corneal topography was normal, but the left side could not be detected. A ultrasound corneal thickness scanner measured the central corneal thickness of 567 μ m on the right side, and no thickness value was detected on the left side due to corneal scar. The peripheral corneal thickness of both eyes was similar (comparison between right and left eyes: 607 and 603 μ m on the upper side, 605 and 595 μ m on the lower side, 607 and 598 μ m on the nasal side, and 570 and 600 μ m on the temporal side, respectively). Ocular B-ultrasound showed that the axial length of the eye was 23.0 mm in the right eye and 23.3 mm in the left eye, the anterior chamber depth was 2.9 mm, and the lens thickness was 3.3 mm in the right eye and 3.9 mm in the left eye. The structure of the right eye was normal, and the lens of the left eye was opaque. Ultrasound bioscopy revealed a central thinning of the cornea in the left eye, protruding forward, flattened iris, open angle, and enhanced echo of the posterior capsule of the lens, protruding posteriorly. Left corneal endothelial cell count 2322.4/mm²Hexagonal cells accounted for 76%. The visual electrophysiological examination of the right eye was normal, the A wave and ops wave of the left eye were low, and the graphic visual evoked potential was not drawn out, which indicated that the left eye had hypovascular function and poor visual conduction. The whole body examination showed no abnormalities. Diagnosis: Left eye posterior lens conus, keratoconus (degenerative stage III), posterior subcapsular cataract, amblyopia.

The patient was a 23-year-old male. On November 23, 2014, he had a routine physical examination in Changchun Aier Eye Hospital. The left eye has poor visual acuity since childhood, 2 years after strabismus correction surgery. Eye examination: the eye position of both eyes is in the right position; Visual acuity was 1.0 for the right eye and 0.04 for the left eye (uncorrectable); IOP was 17 mmHg (1 mmHg =0.133 kPa) in the right eye and 15 mmHg in the left eye; Anterior segment of left eye normal; Right eye normal. For the fundus of the left eye, seeQuintessence Picture 1The left eye OCT image is shown inQuintessence Picture 2。 Clinical diagnosis: congenital retinal fold in left eye; Macular ectopia of the left eye.

The patient was a 38-year-old male. Because of blurred vision in both eyes for half a year, he went to the Department of Ophthalmology, People's Hospital of Wuhan University. The patient had no family history of disease and no past history. Eye examination: corrected visual acuity was 0.6 for the right eye and 0.8 for the left eye; Anterior segment examination of both eyes showed no obvious abnormalities. The fundus examination of both eyes is shown inQuintessence Picture 1AndQuintessence Picture 2For the examination of the multispectral fundus stratification imaging system, seeQuintessence Picture 3。 Clinical diagnosis: vascular striation in both eyes.

The patient was a 47-year-old female. Due to the progressive decline of right eye vision with poor night vision for 3 years, he went to the Department of Ophthalmology of the 401 Hospital of the People's Liberation Army. Eye examination: visual acuity was 10 cm index in the right eye and 1.0 in the left eye; IOP normal; Anterior segment examination of both eyes showed no obvious abnormalities; For fundus examination, seeQuintessence Picture 1。 Clinical diagnosis: retinitis pigmentosa of the right eye (monocular).

The patient was a 21-year-old male. Because the visual acuity of his left eye decreased for more than 2 months, he went to Tianjin Eye Hospital. Eye examination: naked eye visual acuity is 1.0 in the right eye and anterior index in the left eye (uncorrectable); Anterior segment examination of both eyes was roughly normal; Right fundus examination showed no obvious abnormalities; For the left fundus, seeQuintessence Picture 1。 For the OCT examination, seeQuintessence Picture 2。 Clinical diagnosis: Retinal viniform hemangioma of left eye; Macular hemorrhage in the left eye.

Ataxia-telangiectasia mutated(ATM) gene could cause ataxia telangiectasia which is an autosomal recessive disease. The ATM protein kinase encoded by the ATM gene mainly distributed in nucleus as a master regulator of the DNA damage response and apoptosis via cell signaling pathways. The ATM kinase plays a key role in the pathogenesis of cellular senescence and tumor genesis. Recently, some studies have indicated that ATM protein kinase is involved in pathological neovascularization, suggesting that it could be a novel potential therapeutic target in diseases associated with pathological angiogenesis.(Chin J Ophthalmol, 2015, 51:391-394)

There are a variety of genetic eye diseases. In the past years, many methods such as linkage analysis and association analysis have been used to study these diseases and lots of achievements have been made. With the development of the second-generation sequencing technology, DNA sequencing has become much more efficient and cheaper. Exome trapping, combining with the second-generation sequencing technology, has become efficient and accurate means to sequence DNA and screen disease-causing genes. This review outlines the research progresses in eye inherited diseases, the methodological characteristics of second-generation sequencing and exome trapping and their applications in genetic eye diseases.(Chin J Ophthalmol,2015,51:395-400)