Volume 55 · Issue 10 · 2019

This issue focuses on the research progress of fundus diseases. The responsible editorial committee responsible for the planning, composition and review of this issue is Professor Xu Xun.

The concern of high myopia in adolescents is increasingly prominent, because of the high prevalence and early onset of myopia in younger children. High myopia increases the risk of various fundus complications, resulting in serious damage to the vision of the working population. The mechanisms underlying the fundus pathology in high myopia remain unknown, although some studies have indicated the initial thinning of the choroid during the myopia progression might count a lot. The thinning of the choroid would influence the blood supply of the retina and sclera and accelerate the progression of myopia to high myopia, inducing the pathologic changes of the fundus. Since the treatment for pathological myopia is limited and cannot reverse the already existed visual impairment, preventive measures are necessary, including the attempts to delay the onset of myopia, to retard progression from mild myopia to high myopia and to retard the pathological changes of high myopia. Future researches should strengthen the understanding of the characteristics of pathologic changes of myopia, establish a predictive index system and a health management system to monitor early pathological changes, and promote early detection and intervention, so as to prevent fundus complications related to high myopia in multiple ways and avoid blindness and visual impairment caused by pathological fundus changes of myopia. (Chin J Ophthalmol, 2019, 55:721-725)

Retinoblastoma (RB) is the most common intraocular malignant tumor that seriously endangers the life and visual function of infants and young children. In order to standardize the clinical diagnosis and treatment of RB, the Fundus Disease Group and Ophthalmology and Orbitology Group of Ophthalmology Branch of Chinese Medical Association, together with the Ophthalmology Group of Pediatrics Branch of Chinese Medical Association, organized relevant domestic experts, and after repeated discussions, put forward the standardized opinions on the diagnosis and treatment of RB in China, which can be used by ophthalmologists for reference in clinical practice. (Chinese Journal of Ophthalmology,2019，55：726-738）

To analyze surgical outcomes by internal limiting membrane peeling and air tamponade in large idiopathic macular holes (IMHs) and the correlation between the minimal diameter and the primary closure rate.

Retrospective study. A total of 282 patients (300 eyes) with IMHs larger than 400 μm who underwent vitrectomy and internal limiting membrane peeling in Beijing Tongren Hospital from July 2015 to January 2019 were enrolled, including 56 males (61 eyes) and 226 females (239 eyes) with an medium age of 65(62, 68) years. Before July 2016, gas tamponade was applied while after that, air tamponade was used. The minimal diameter of the IMH was measured. IMHs were divided into intervals every 50 μm by minimal diameter, and the primary closure rate of the two tamponades were compared between intervals by Chi-square test. The receiver operating characteristic (ROC) curve was drawn to show the correlation between the minimal diameter and the primary closure rate by air tamponde.

The mean minimal diameter of all the IMHs was (615.7±126.0)μm. In general, the primary closure rate was 91.7% (275/300), and the BCVA at last visit (0.5(0.3, 0.7)) improved significantly (P<0.001) comparing to the preoperative one (0.1(0.05, 0.2)). A total of 187 eyes with air tamponade exhibited a primary closure rate of 88.2%, which was significantly lower (P=0.005) than that with gas tamponade (97.3%). For IMHs with air tamponade, the optimal closure rate was 100% among all intervals; from the interval of (650, 700)μm on, the primary closure rates of every interval gradually decreased and were significantly lower than the optimal one (P<0.05) respectively; the ROC curve revealed that IMHs larger than 664.5 μm tended to exhibit a smaller chance of primary closure. For IMHs ≤650 μm, the two tamponades exhibited comparable primary closure rate (96.1% for air, 100.0% for gas, P=0.17), while for IMHs>650 μm, air tamponade (71.2%) presented significantly lower rate (93.5% for gas,P=0.002). IMHs ≤650 μm exhibited significantly better BCVA compared to those larger ( P<0.01), no matter which tamponade was applied. In IMHs ≤650 μm, BCVA exhibited no significant difference between the two tamponades, so as in IMHs>650 μm.

For IMHs with air tamponade, the minimal diameter is closely related to both the primary closure rate and the postoperative BCVA. IMHs>650 μm exhibited evidently poorer anatomical and functional outcomes compared with those ≤650 μm, which suggested that maybe other techniques for the internal limiting membrane could be applied to improve surgical outcomes for these large IMHs.(Chin J Ophthalmol, 2019, 55:739-746)

To investigate the characteristics of morphological changes of inner retinal layer after internal limiting membrane peeling in macular hole surgery.

Retrospective case study. Patients with idiopathic macular hole from 2015 to 2018 underwent vitrectomy+internal limiting membrane peeling (inverting)+ gas tamponade in China-Japan Friendship Hospital were investigated. A total of 19 eyes (17 patients) were enrolled, including 4 males (4 eyes) and 13 females (15 eyes). The average age was 62.74±5.25 years. Optical coherence tomography (OCT) was used to obtain the topographic maps of retinal thickness, the thickness of retinal ganglion cell complex and probability maps, and the Angio/en-face maps of macular retina. The characteristics of the morphological changes of the inner retinal were comprehensively analyzed.

Among 19 eyes, 9 eyes had internal limiting membrane peeling, 8 eyes had lotus-like internal limiting membrane inverting, and 2 eyes had the uper180 degrees internal limiting membrane inverting. The minimum diameter of macular hole was (543.06+220.17) μm and the maximum diameter was (947.18+319.12) μm. The follow-up time was (21.05+9.66) months, and the visual acuity was 0.45+0.35 at the last follow-up. In the 19 eyes, all the macular holes were closed postoperatively and dissociated optic nerve fiber layer appearance (DONFL) and concentric macular dark spots (CMDS) all showed, as well as mGCC thinning. The changes of CMDS and mGCC in 2 eyes in the uper180 degrees internal limiting membrane inverting group were mainly seen in the upper retina and in the remaining 17 eyes were seen diffused around the macula, which roughly corresponded to the extent of internal limiting membrane peeling. Two eyes showed clear decrease of retinal capillary density on Angio/map.

Long-term morphological changes of the inner retinal after internal limiting membrane peeling in macular hole surgery are obvious. In addition to the appearance changes like DONFL and CMDS, the macular ganglion cell complex (mGCC) is also involved. (Chin J Ophthalmol, 2019, 55:747-756)

To observe changes in foveal avascular zone(FAZ) and capillary plexus in idiopathic macular epiretinal membrane (IMEM) in optical coherence tomography angiography (OCTA) and analyze their correlation with the visual acuity.

Cross-sectional study. 42 patients (15 Males and 27 females, age 64.8) from the Eye Hospital of Wenzhou Medical University were included with 51 eyes diagnosed as IMEM (IMEM group), and 23 normal eyes (9 Males and 14 females, control group). All patients received the examination of fissure lamp combined with fundus pre-set lens, best corrected visual acuity (BCVA), OCT angiography (OCTA) and fundus photo. OCTA was performed on 3 mm× 3 mm sections centred on the fovea. The software automatically measured the superficial capillary plexus (SCP) and deep capillary plexus (DCP) vessel density(VD) and retinal thickness(RT) and FAZ area. The IMEM eyes were compared with the normal eyes and correlation between the parameters of OCTA and BCVA was analyzed in IMEM. Independent-sample t test and MannWhitney test were used for comparison between groups, and Spearman test was used for correlation analysis.

LogMAR BCVA in the IMEM group was 0.40(0.15, 0.70), in the control group was 0.10(0.05, 0.22). FAZ area of IMEM group was (0.09±0.05) mm², while that of control group was (0.34±0.13)mm².Compared with the control group, in IMEM group, the BCVA was worse (Z=-4.443, P<0.001), FAZ area was smaller (t=-9.198, P<0.001), RT was increased (P<0.001), The foveal DCP and SCP vessel density was increased (t=4.280, 9.079, P<0.01), The parafoveal DCP vessel density was decreased (P<0.05), The parafoveal SCP vessel density was decreased in superior, inferior and nasal side (t=−2.759, Z=−3.998, Z=−2.108; P<0.05). The BCVA was negatively correlated with FAZ area (r=-0.337, P=0.017), positively correlated with center macular thickness (r=0.324, P=0.020). The BCVA was no correlated with foveal VD and parafoveal DCP vessel density (P>0.05), but correlated with SCP vessel density(P<0.05).

In the IMEM eyes the BCVA was worse, FAZ area was smaller, foveal vessel density was increased and the parafoveal vessel density was decreased compared with the normal eyes. The smaller the FAZ area, the smaller foveal SCP vessel density, the poorer BCVA. There was no correlation between BCVA and DCP vessel density. Changes in VD in IMEM eyes may lead to changes in vision. (Chin J Ophthalmol, 2019, 55:757-762)

To screen the retinopathy in HIV/AIDS patients with both non-mydriatic ultra-wide-field (UWF) retinal imaging and mydriatic fundus examinations with the Superfield lens and a slit lamp biomicroscope, and to evaluate the consistency of two methods and provide reference for future clinical screening work and even technological innovation (such as telemedicine screening and artificial intelligence).

Cross sectional study. One hundred and fifty-eight eyes of 80 HIV-positive patients from the Ophthalmology Department of Beijing Youan Hospital were enrolled in this prospective observational study. All patients underwent comprehensive ophthalmological examination. A single image was obtained from each eye using the UWF fundus imaging system (Daytona, Optos, Dunfermline, UK), and then a dilated fundal examination with the Superfield lens was conducted by another expert. The possible type and location of the lesion with these two methods was recorded respectively. The consistency was compared using the detection rate and Kappa value.

Fifty-two patients (65%) had fundus changes, and 28 patients (35%) were normal. Seventy-nine eyes (50%) were normal and 79 eyes (50%) had fundus lesions. Sixty-one eyes (77.2%) had HIV-related fundus lesions, while 18 eyes (22.8%) had non-HIV-related fundus lesions. Fifty-two eyes (65.8%) suffered posterior or posterior involving lesions, and 27 eyes (34.2%) suffered isolated peripheral lesions. The detection rate of UWF retinal imaging and slit lamp biomicroscopy with the Superfield lens was 17.7% (28/158) and 18.4% (29/158) (P=1.000>0.05) for HIV-related microvascular retinopathy, 8.2% and 8.2% (13/158) (χ²=158.00, P=1.000) for cytomegalovirus retinitis (CMVR), 36.1% and 36.1% (57/158) (χ²=71.066, P=1.000) for HIV-related fundus lesions, 41.8% (66/158) and 47.5% (75/158) (χ²=63.514, P=0.136) for fundus lesions, 33.5% (53/158) and 31.0% (49/158) (χ²=108.268, P=0.388) for posterior/posterior involving lesions, and 6.4% (10/158) and 16.5% (26/158) (χ²=42.001, P=0.000) for isolated peripheral lesions, respectively. In general, the consistency of these two methods was moderate in detecting fundus lesions (Kappa=0.630), HIV-related fundus lesions (Kappa=0.671), HIV-related microvascular retinopathy (Kappa=0.551), and isolated peripheral lesions (Kappa=0.450). According to the fundus location, the two methods showed high consistency in the detection of posterior/posterior involving lesions (Kappa=0.826>0.75) and perfect consistency for CMVR (Kappa=1.0).

The UWF retinal imaging system and the Superfield lens showed reasonable consistency in fundus screening in HIV/AIDS patients, especially for CMVR, or lesions in the posterior pole. (Chin J Ophthalmol, 2019, 55:763-768)

To identify differentially expressed proteins between the patients with proliferative diabetic retinopathy (PDR) and vitreous floaters, and explore treatment target for PDR based on isobaric tags for relative and absolute quantification (iTRAQ) LC-MS/MS Proteomics.

Vitreous samples were collected from 28 eyes of patients with PDR and 4 eyes with vitreous floaters, which served as controls. For quantitative proteomics, vitreous samples were combined and proteins extracted and labeled with iTRAQ peptide-tagging reagents. Samples were fractionated by liquid chromatography (LC), analyzed by tandem mass spectrometry (MS/MS) and Gene Ontology (GO) analyses performed on differentially expressed proteins identified in the PDR samples.

In the PDR vitreous, 26 proteins were identified that were differentially expressed when compared to the controls. Of these, 7 showed a significant increase (P<0.05) and 19 a significant decrease (P<0.05)in expression in PDR patients. These included some high abundance proteins including Retinoic acid receptor reactive protein 2 (PDR 1=85.0, PDR 2=83.0, Control 1=119.6, Control 2=120.2, FC=0.710, P=0.001), Semaphorin-4B(PDR 1=64.4, PDR 2=68.8, Control 1=135.4, Control 2=146.0, FC=0.473, P=0.023), Apolipoprotein B (PDR 1=104.4, PDR 2=106.6, Control 1=89.0, Control 2=85.3, FC=1.211, P=0.024), and Heat shock protein 70 (PDR 1=69.3, PDR 2=75.0, Control 1=137.7, Control 2=138.3, FC=0.523, P=0.026), which are closely related to the pathological mechanism of PDR. GO analysis clustered the differentially expressed genes into three major functional domains: Biological Processes, Molecular Function and Cellular Component. Differential gene expression was found in the categories of cellular metabolism, organonitrogen compound and carbohydrate derivative metabolic processes, transferase activity and transmembrane signaling receptor activity. KEGG Pathway analysis indicate that Chemerin signaling through Akt, Sema4B signaling via PI3K, and HIF-1α signal pathways were all altered in the PDR samples.

In this study we identified variations in expression of genes extensively involved in key biological processes in the retina including neovascularization, cellular metabolism and transmembrane signaling, which provide new insights into the pathophysiology of PDR. Extracellular matrix was degraded and endothelial cell migration was induced by Chemerin, in addition, the destruction of blood-retinal barrier and neuronal apoptosis were induced by ApoB. Chemerin and ApoB accelerated the development of PDR. Sema 4B participated in vascular protection, HSP70 conducted anti-apoptosis. These two cytokines protected the retinal neurovascular in PDR patients. Therefore, Chemerin, Sema 4B, ApoB and HSP70 may be the treatment target for PDR. (Chin J Ophthalmol, 2019, 55:769-776)

To evaluate risk factors for visual field (VF) loss progression in primary open-angle glaucoma patients.

A prospective nested case-control study. Patients were collected from the Wenzhou glaucoma progression study in the Eye Hospital of Wenzhou Medical University during March 2014 and April 2018. In this study, the eyes were divided into a progression group and a non-progression group using the glaucoma progression analysis methods to analyze the risk factors for glaucomatous VF loss progression. Axial length (AL) and central corneal thickness (CCT) were measured using the Lenstar LS900. The baseline, fluctuation (standard deviation), mean, maximum, minimum and range of intraocular pressure (IOP) during the follow-up period were determined based on IOP measured at each follow-up. The IOP measurements were included from the baseline to the last visit (for the non-progression group), or to the visit at which VF loss progression was determined (for the progression group). The independent sample t-test, Mann-Whitney U inspection and Cox proportional hazards models were used for statistical analysis.

A total of 140 patients (140 eyes) were enrolled, including 67 males and 73 females. There were 19.3% of the eyes (27 of 140 eyes) showing VF loss progression. The median time to the endpoint for progression was 24.0 (16.0, 40.0) months. The AL in the progression group and non-progression group were 23.58 (23.05, 24.24) mm and 23.91 (23.10, 24.91) mm (P=0.111). The CCT in the two groups were 531.0 (512.0, 565.0) μm and 535.0 (518.5, 552.0) μm, respectively ( P=0.897). The baseline age in the progression group and non-progression group was 71.0 (68.0, 74.0) years and 68.0 (58.0, 72.0) years, respectively (Z=-2.872, P=0.004). The slope of visual field index in the two groups was -3.50 (-7.10, -1.80)%/year and 0.40 (-0.60, 1.40)%/year, respectively (Z=-6.823, P<0.01). The mean IOP during the follow-up was (16.2±2.7) mmHg (1 mmHg=0.133 kPa) in the progression group and (15.1±2.4) mmHg in the non-progression group (t=-2.215, P=0.028). The IOP fluctuation in the progression group and non-progression group was (2.6±1.3) mmHg and (2.0±0.7) mmHg, respectively (t=-2.175, P=0.038). In the multivariate model, older baseline age (HR=1.080; 95%CI:1.019-1.143), higher baseline IOP (HR=1.120; 95%CI:1.016-1.236), higher mean IOP (HR=1.145; 95%CI:1.001-1.309) and higher IOP fluctuation (HR=1.750; 95%CI:1.193-2.566) were all significantly predictive risk factors for glaucomatous VF loss progression. Longer AL (HR=0.725; 95%CI:0.532-0.988) was a protective factor against VF loss progression. However, CCT was found to be not associated with VF loss progression.

Baseline age, baseline IOP, mean IOP, IOP fluctuation and shorter AL are found to be risk factors for glaucomatous VF loss progression among eyes with primary open-angle glaucoma in Wenzhou. (Chin J Ophthalmol, 2019, 55: 777-784)

An 8-year-old girl came to the clinic because of left eye pain with visual loss. Ophthalmic examination revealed diffuse spotted staining of the central epithelium of the cornea in both eyes, obstruction of the opening of the meibomian gland, redness and swelling of the eyelid margin, eyelash loss, rough skin of both eyelids, and eyebrow loss. General physical examination: no hair, absent teeth, skin keratosis, the mother of the child had the same symptoms and signs, and was diagnosed as congenital ectodermal dysplasia. (Chinese Journal of Ophthalmology,2019，55：785-787）

A 47-year-old male was seen for pain in the right eye, photophobia with visual loss for 2 months. The patient had fish-scale-like changes in the skin of the whole body, baldness, absence of eyebrows and eyelashes, atresia of meibomian gland openings in both eyelids, and perforated corneal ulcer in the right eye. Follicular ichthyosis with photophobia and alopecia syndrome was diagnosed. Right eye conjunctival flap covering and double eyelid margin fusion were performed in ophthalmology department. Moisturizing and lubricating eye solution and eye ointment were used, and good results were achieved. (Chinese Journal of Ophthalmology,2019，55：788-789）

Surgeon IntroductionSun Xiaodong, Professor (Chief Physician), Vice President and Deputy Director of Ophthalmology Department of the First Affiliated People's Hospital of Shanghai Jiaotong University. He is a member of the Ophthalmology Branch of Chinese Medical Association, a member of the Ophthalmologist Branch of Chinese Medical Physicians Association, a distinguished professor of "Yangtze River Scholar" of the Ministry of Education, a chairman-designate of the Ophthalmology Branch of Shanghai Medical Association, a member of the American Society of Retina Specialists, and an international member of the American Academy of Ophthalmology.

The patient was a 17-year-old male. He was seen in the Department of Ophthalmology of Leshan People's Hospital of Sichuan Province due to decreased visual acuity in his left eye and occlusion of visual objects for 6 days. Six days ago, the patient was accidentally hit by a basketball in his left eye while playing basketball, and one day later, he experienced visual decrease with visual obstruction. The patient was previously in good health. The whole body examination showed no obvious abnormalities. Eye examination: corrected visual acuity was 1.0 for the right eye and 0.1 for the left eye; IOP was 19 mmHg (1 mmHg =0.133 kPa) in the right eye and 18 mmHg in the left eye; The cornea of both eyes is transparent, the anterior chamber is deep, and the lens is transparent; The retina of the right eye is flat and leopard-shaped, with foveal reflection visible, and the leopard-shaped fundus of the left eye, with a huge retinal hole visible from 9:30 to 14:30. The detached retina flips to cover the optic disc and macular area, like a curtain (Quintessence Picture 1）。 Clinical diagnosis: Rhegmatogenous retinal detachment (giant hiatus) in left eye; Refractive error in both eyes.

Pathological myopia refers to high myopia with fundus pathological changes. Choroidal neovascularization is one of its serious complications, and also the main cause of visual loss. Currently, the first-line treatment is anti-VEGF treatment, with good efficacy, high safety, good prognosis, and other advantages of vision. Commonly used anti-VEGF drugs include bevacizumab, ranibizumab, aflibercept, and conbercept. The main treatment strategies include 1+pro re nata and 3+pro re nata, and the standard of REPAIR test is often used to evaluate the re-injection. This article reviews the advantages of anti-VEGF therapy, drug selection, treatment strategy, and re-injection criteria. (Chin J Ophthalmol, 2019, 55:791-795)

As one of the important organs of human body, visual organ is inseparable from other organs and systems in the whole body. With the continuous progress of medicine, it has been found that many systemic diseases can have ocular symptoms and signs, and even the first diagnosis of eye diseases, which requires ophthalmologists to have solid basic medical knowledge and rich clinical experience, not only to be familiar with ophthalmology professional knowledge, but also to understand the relationship between various diseases in the whole body and the eye, so as to achieve early diagnosis and treatment, so that patients can obtain satisfactory treatment results. This article summarizes several systemic diseases of ophthalmology, such as sarcoidosis, lymphoma and neurological diseases, in order to provide reference for the clinical work of ophthalmology. (Chinese Journal of Ophthalmology,2019，55：796-800）