Volume 55 · Issue 12 · 2019

This issue focuses on the research of ocular surface diseases. The responsible editorial committee responsible for the planning, composition and review of this issue is Professor Liu Guoguo.

Dry eye has become a common disease in ophthalmic clinics. With the continuous development and application of examination and treatment equipment, doctors′ understanding of dry eye has improved as well as the diagnosis and treatment level of dry eye. However, there are some problems in the diagnosis and treatment of dry eye so far. Doctors rely too much on equipment to help diagnosis and ignore routine eye examinations with the ophthalmic special examinations prescribed usually being lack of definite purposes. The analysis of results is not scientific. The selection of treatment methods is not careful enough. Therefore, standardized diagnosis and reasonable treatment are the goals that dry eye clinics are required to achieve. During the clinical practice, doctors should attach importance to history taking and the analysis of clinical symptoms, strengthen the basic examination of dry eye, gradually expand the scope of examination and make a reasonable and targeted treatment plan. (Chin J Ophthalmol, 2019, 55: 881-884)

Dry eye is one of the most common eye diseases characterized by disturbance of tear film homeostasis and a series of ocular discomforts. Discrepancy of ocular subjective symptoms and objective signs, especially unexplained severe symptoms without visible signs has been a long-time confusion for ophthalmologists. Functional disorder is a medical condition that impairs normal functioning of bodily processes due to autonomic nervous dysfunction caused by cerebral cortical dysfunction, but at the exterior, there is no appearance of abnormality. Clinical manifestations are the disease symptoms with a lack of exact physical signs and examination results to confirm the diagnosis. According to the definition and characteristics of functional disorder, we put forward the concept of functional dry eye. We assume that those patients with dry eye symptoms but without detectable signs could be classified into such a functional dry eye subtype. The possible mechanism, clinical manifestations, and treatment strategies are further discussed. (Chin J Ophthalmol, 2019, 55: 885-890)

Keratoconus is a blinding eye disease that tends to occur in adolescence and is characterized by dilation and thinning of the cornea with a conical protrusion forward. The diagnostic criteria and treatment of keratoconus in China are not uniform, and there are still many controversies. In recent years, new diagnostic equipment and diagnosis and treatment technology in ophthalmology are developing continuously. It is very necessary to standardize the diagnosis and treatment of clinical keratoconus in China. Therefore, the Keratology Group of Ophthalmology Branch of Chinese Medical Association has formulated this consensus after full discussion, in order to provide guiding opinions for clinical work.(Chinese Journal of Ophthalmology, 2019, 55:891-895)

With the increasing incidence of myopia in China and the continuous progress of various treatment techniques, laser corneal refractive surgery has become one of the important ways to correct refractive errors. Rational medication in perioperative period is an important link to ensure the success of surgery and reduce complications. However, there is no relevant unified understanding and method at home and abroad. Therefore, the Ocular Microcirculation Refraction Committee of China Microcirculation Committee and experts from relevant professional groups of Ophthalmology Branch of Chinese Medical Association reached a consensus after discussion, so as to further standardize the perioperative medication of laser corneal refractive surgery in China and improve the quality of surgery.(Chinese Journal of Ophthalmology, 2019, 55:896-903)

To study the safety and efficacy of topography-guided customized excimer laser subepithelial ablation combined with accelerated collagen cross-linking technique in treatment of early keratoconus.

Ninteen patients(20 eyes) (13 males 14 eyes, and 6 females 6 eyes), aged 12 to 44 years (24.7±8.0) were diagnosed as keratoconus by three-dimensional corneal topography and tomography, clinical history and examinations, and classified as KC1~KC3. Based on the classical excimer laser subepithelial keratomileusis (LASEK) method, topography guided laser ablation was performed with an excimer laser system (WaveLight EX500). After laser ablation, the corneal stromal bed was immersed with 0.1% riboflavin for 10 minutes, and then was irradiated by ultraviolet light (Avedro KXL) at 30 mW/cm² for 4 minutes. All the patients were followed up for more than 12 months. The uncorrected visual acuity (UCVA), diopter, best corrected visual acuity (BSCVA), corneal topography, central corneal endothelial cell density (ECD), hexagonal cell percentage (HEX), coefficient of variation (CV) and other indicators were observed. For normal distribution variables, Dunnett-t test was used before and after operation, and Wilcoxon test was used for variables with abnormal distribution. And the complications were recorded.

There was no loss of BSCVA at 12 months postoperatively, 20% of the eyes had no change of BSCVA, and 15% of the eyes gained 1 line of BSCVA, 15% of the eyes gained 2 lines of BSCVA, 50% of the eyes gained 3 lines and more of BSCVA. There was no significant difference in UCVA, BSCVA, manifest refractive spherical equivalent (MRSE) and the cylinder at 3 months postoperatively (P>0.05). The BSCVA were significantly improved at 6 and 12 months postoperatively compared with those before operation (t=3.095, 3.079, <0.05). Although there was no significant difference in UCVA and MRSE, the cylinder was significantly reduced at 6 and 12 months postoperatively ( t=-2.890, -2.435, P<0.05). Apex curvature (Kapex) and mean pupil power (MPP) within 4.5mm of central cornea decreased significantly (Z=-2.903, P<0.01; Z=-2.667, P<0.01). Even though the thinnest corneal thickness decreased from pre-operational (461.9±31.1) μm to post-operational (416.6±27.0) μm ( Z=-3.059, P<0.01), the cornea became regular with keratometric asymmetry index of anterior corneal surface decreased (Z=-2.667, P<0.01). The corneal optical quality parameters were improved. There was no significant difference in ECD, HEX and CV at 12 months postoperatively (P>0.05). Twelve months after operation, grade 0, 0.5, 1 and 2 haze were seen on 20%, 55%, 20% and 5% corneas respectively.

The topography guided excimer laser ablation combined with accelerated corneal collagen cross linking is safe and effective in treatment of early stage keratoconus. It can significantly improve corneal regularity while preventing keratoconus progression, so as to improve the best corrected visual acuity postoperatively. (Chin J Ophthalmol, 2019, 55: 904-910)

To investigate the diagnosis of normal cornea, subclinical keratoconus and keratoconus by artifical intelligence.

Diagnostic study. From January 2016 to January 2019, who admitted to Tianjin Eye Hospital from 18 to 48 years old, with an average of (28.4±8.2) years of myopia patients in 2 018 cases. Two experienced ophthalmologists labeled keratoconus, subclinical keratconus and nomal cornea based on the topography. The data of 80% (1 615 cases) patients were randomly selected as the training set by computer random sampling method, and the data of 20% (403 cases) patients were used as the verification set. Using the Gradient Boosting Decision Tree (GBDT) algorithm to extract 28 corneal parameters, and establish an algorithm model to diagnose the corneal condition of the patient, verify the diagnostic accuracy of the model by using the 10-fold cross-validation method, and evaluate the model using the receiver operating characteristic curve. Sensitivity and specificity with the original labeling and ophthalmic resident labeling.

The diagnostic accuracy of the model was 95.53%. The area under the receiver operating characteristic curve (AUC) of the validation set was 0.996 6. The accuracy of the model for diagnosis of subclinical keratoconus and normal cornea was 96.67%, the AUC of the validation set was 0.993 6; the accuracy of diagnosis of keratoconus and normal cornea was 98.91%, and the AUC of the validation set was 0.998 2. The diagnostic accuracy of the model is 95.53%, which is significantly better than the resident′s 93.55%.

The model established by artifical intelligence can diagnose the subclinical keratoconus with high accuracy, which can greatly improve the clinical diagnosis efficiency and accuracy of young and primary ophthalmologists. (Chin J Ophthalmol, 2019, 55: 911-915)

Introduce the surgical techniques of bridge-shaped flap penetrating keratoplasty and whole lamellar keratoplasty with corneoscleral limbal and the comparison of therapeutic effects on keratoglobus.

Five patients (eight eyes) with keratoglobus from January 2010 to December 2015 were included. Three eyes received bridge-shaped flap penetrating keratoplasty (two eyes with corneal penetrating injury due to trauma, one eye with descemet′s membrane detachment) and five eyes received whole lamellar keratoplasty with corneoscleral limbal.

The patients (four male, one female) aged 3 to 67 years old. Three younger patients were complicated with blue sclera. The visual acuity of all the patients pre-operation were lower than 0.05. The average visual acuity after whole lamellar keratoplasty (LKP) surgery was 0.2, while the average visual acuity after bridge-shaped flap penetrating keratoplasty (PKP) was 0.5. The corneal epithelium of the three eyes received bridge-shaped flap PKP surgery was completely healed within a week with no recurrence of corneal epithelial defect. Whereas one eye after whole LKP surgery arised persistent corneal epithelial defect and healed after blepharorrhaphy. The corneal epithelial of another eye after whole LKP surgery healed slowly and was completely healed after wearing a bandage lens on corneal for 2 months. The corneal epithelial of the remaining three eyes after whole LKP surgery was completely healed within a week. Two eyes received bridge-shaped flap PKP surgery arised corneal graft rejection 2 months after operation and recovered after anti-rejection treatment. No corneal graft rejection arised in the patients receiving whole LKP surgery.

The whole lamellar keratoplasty with corneoscleral limbal could effectively reinforce corneal, avoid corneal penetrating injury caused by minor trauma, and improve visual acuity in keratoglobus whose corneas were gradually thinning and corrected vision cannot be improved. The patients with corneal perforating injury or descemet′s membrane detachment could obtain good visual prognosis receiving bridge-shaped flap penetrating keratoplasty. (Chin J Ophthalmol, 2019, 55:916-922)

To discuss effect of autologous simple limbal epithelial transplantation (SLET) performed for unilateral limbal stem cell deficiency (LSCD).

Retrospective case study. In this retrospective study, records of 7 patients (7 eyes) who had undergone autologous SLET for unilateral LSCD, with a minimum of 6 months of follow-up, were reviewed. Demographic details, etiology of LSCD, duration between ocular burn and SLET, prior surgery performed, presence or absence of symblepharon, pre-and post-operative visual acuity, and complications were noted.

Seven eyes of 7 patients underwent autologous SLET. With a follow-up of 6 months, a completely epithelialised and stable corneal surface was obtained in all recipient eyes. Visual acuity improved in all patients, while none of the eyes developed any complications.

Autologous SLET is an effective and safe modality for treatment of unilateral LSCD. Clinical success rates and visual acuity improvement are equal to or better than those reported with earlier techniques. (Chin J Ophthalmol, 2019, 55:923-927)

Comparison of the permeability between the rabbit cornea and sclera ex vivo by determining the concentration of gatifloxacin using LC-MS/MS method, which may provide the basis for a new route of drug administration.

Experimental study. The permeability of the cornea and sclera in healthy male New Zealand rabbits was evaluated by using Franz diffusion pool. We chose both gatifloxacin ophthalmic solution and gel as the test drugs, and calculated the cumulative permeation amounts (Qn), apparent permeability coefficient(P_app).

The linear range of gatifloxacin was 5-1 000 ng/ml. The intra-day and inter-day precision was 1.7% -2.8% and 1.0% - 2.3%. Q_n and P_app of gatifloxacin ophthalmic solution in cornea and sclera ex vivo were 177.57, 517.52 μg/cm ² and 4.34, 12.51 cm/s respectively, whereas that of gatifloxacin ophthalmic gel were 151.87, 411.05 μg/cm ² and 3.66, 9.21 cm/s.

This validated method could be applied to determine the gatifloxacin. The cumulative permeation amounts and apparent permeability coefficient of sclera are significantly higher than that of cornea for both ophthalmic solution and gel, suggesting that the development of a new route of drug administration based on sclera may have potential advantage. (Chin J Ophthalmol, 2019, 55: 928-932)

To study the effects of human umbilical mesenchymal stem cells (HUMSCs) exosomes on the proliferation and apoptotic as well as migration of human retinal pigment epithelial cells (HRPE) in hypoxia, and explore its mechanism.

Direct adherent culture was adopted to cultivate umbilical cord mesenchymal stem cells and amplified to the fourth generation. Markers on the cell surface were identified by flow cytometry. Culture medium was collect without serum from the 4th generation umbilical cord mesenchymal stem cells. Exosomes were separated and extracted, then the ultrastructure was observed under electron microscope and examined expression of CD63 and CD9 protein by Western blot method with isolated and extracted exosomes. HRPE was cultivated in vitro culture, proliferation was detected at the time point of 0, 1, 2, 3, 4, 5 d with MTT assay under hypoxic condition. Meanwhile, the cell migration was quantified by Wound-Healing Assay under hypoxic condition at 0, 24, 48 and 72 h respectively combined with apoptosis test. The HRPE cells in the growth period were divided into 5 groups: the control group, the hypoxia group and the pretreated exosomes group (100, 200, 300 μg/ml). In all groups, apoptosis was observed by Annexin V/PI dual-dye flow cytometry after 48 h′s incubation. Proliferation was observed by MTT assay and the migration was observed with Wound-Healing Assay.

Flow cytometry detection of the surface marker of HUMSCs in the 4th generation showed strong positive expression of CD105, CD73, CD90. It was suggested that HUMSCs with isolated culture had MSC specific phenotype with duction of lipids and osteoblasts in vitro. The separated exosomes were observed with spherical membranous structures in different sizes by scanning electron microscopy, and Western blot detected positive expression of CD63 and CD9. In vitro culture of HRPE detected by MTT assay for cell proliferation at the time of hypoxic 0, 1, 2, 3, 4, 5 d, the results showed that, comparing with time point 0 d, other groups had statistically significant OD values. In the first 2 days, the proliferation ability of RPE cells gradually increased as the time of hypoxia prolonged(1.862±0.135, 2.278±0.244). After 3 d, the proliferation ability of RPE cells gradually decreased(1.419±0.124, 1.599±0.156). Wound-Healing Assay results showed that the migration distance gradually increased as[(29.883±4.504), (36.200±1.928) μm] the time of hypoxia increased from 0 to 72 h. The cells were fully covering at the point of 72 h [(1.223±0.194), (0.430±0.299) μm]. Apoptosis test results showed that the number of apoptotic cells was different(3.628%±1.348%, 20.123%±1.183%) with the extension of hypoxia Oxygen before 2 d from 0 to 72 h. At the time of d3, there were more apoptotic cells(42.290%±3.217%). There is a significant difference from pre-2d.RPE cells were divided into 5 groups: the control group, the hypoxia group and the pretreated exosomes group (100, 200, 300 μg/ml).After 48 h hypoxia incubation, MTT assay results showed that, compared with the control group (1.870±0.499), the number of cell proliferation was significantly increased ( t=-3.116, P<0.05), while compared with the hypoxia group(2.616±0.307), the proliferation number of exosomes was significantly reduced [(2.041±0.115), (1.931±0.205), (1.929±0.025); t=-4.920, -4.540, -5.286, P<0.01], and there was no significant difference between groups with different doses of the exosomes (F=1.181,P>0.05). Annexin V/PI dual-dye flow cytometry was used to observe the apoptosis results. Compared with the control group 1.180%±0.689%, the number of apoptosis in hypoxia group was significantly increased (19.273%±1.194%, t=-32.141, P<0.01), while compared with the hypoxia group, the number of apoptosis in the exosomes was significantly decreased (12.318%±1.087%, 11.878%±1.348%, 11.090%±1.716%; t=-10.547, -10.057, 9.589, P<0.01). There was no significant difference between the groups with different doses of exosomes (F=1.173, P>0.05). Wound-Healing Assay results showed that, compared with the control group(68.047±2.851) μm, the migration distance of the hypoxia group was significantly increased [(13.470±2.255)μm, t=36.778, P<0.01] while compared with the hypoxia group, the migration distance of the exosomes was reduced (33.110±1.774, 24.650±1.175, 26.440±1.674; t=11.766, 10.770, 11.311, P<0.01), and there was no significant difference between the groups of the exosomes (F=1.179, P>0.05).

Human umbilical cord mesenchymal stem cells can effectively inhibit the apoptosis and migration of HRPE cells in hypoxia. It provides a theoretical basis for the research and treatment of RPE related diseases. (Chin J Ophthalmol, 2019, 55: 933-941)

To investigate the safety and efficacy of anterior segment coherence optical tomography (OCT) -guided excimer laser refractive therapy combined with resection of corneal opacity with refractive error.

Retrospective study. From January 2013 to January 2015, a total of 7 cases (12 eyes), aged (30.3±18.0) years, were treated with excimer laser refractive therapy combined with resection of corneal opacity with refractive error in Shandong Eye Hospital. Anterior segment OCT measures the depth of corneal opacity. The refractive cutting is performed first and then the therapeutic cutting is performed. The depth of corneal opacity minus the thickness of corneal epithelium and the refractive cutting depth is the therapeutic cutting depth. The grade of corneal opacity, naked visual acuity, best corrected visual acuity and subjective optometry were recorded at 3, 6 and 12 months after operation.

The degree of corneal opacity was>grade 1 in 12 eyes before operation, and the degree of corneal opacity was ≤ grade 1 in 8 eyes 12 months after operation. The effectiveness index at 3, 6 and 12 months postoperatively was 0.96, 1.04 and 1.04, respectively; The safety indices were 1.10, 1.22, and 1.27, respectively. Compared with the best corrected visual acuity before surgery, the best corrected visual acuity improved by 2 lines in 4 eyes, 1 line in 7 eyes and equal in 1 eye at 12 months after surgery. Preoperative spherical degree (0.29±2.57) D, postoperative 12 months (0.95±1.30) D; The cylinder power was (-2.37 ± 2.48) D before surgery and (-1.23 ± 1.19) D at 12 months after surgery.

Excimer laser refractive therapy under the guidance of anterior segment OCT is safe, effective and reliable for the combined resection of corneal opacity with refractive error.(Chinese Journal of Ophthalmology, 2019, 55:942-945)

A 14-year-old child suffering from ichthyosis vulgaris since childhood came to the doctor because of blurred vision in both eyes. Physical examination showed that there was patchy opacity in the deep stroma of the cornea in both eyes. The detection of the exon encoding the STS gene suggests that the STS gene is completely deleted. Fine sand-like appearance on (or merged extracellular) deep stromal layer cells in front of the elastic layer of the posterior cornea can be seen under a live laser confocal microscope.(Chinese Journal of Ophthalmology, 2019, 55:946-949)

A 63-year-old male was admitted to the hospital with fungal corneal ulcer because of no obvious improvement in antimicrobial treatment in his left eye after chestnut prick wound. Gray-white infiltration of the cornea below the nose can be seen, and pseudopod can be seen; Fungal hyphae images were visible under confocal microscopy. Fungal hyphae and gram-positive filamentous bacteria were detected after tissue smear in the lesion area. The bacteria were identified as Streptomyces by 16S rRNA sequence analysis; After culture, the fungus was identified as Stempunctatus. Streptomyces of the left eye with fungal keratitis was diagnosed. According to the results of drug sensitivity test, the effect of the corresponding antibacterial drugs was good, and there was no recurrence after 5 months follow-up.(Chinese Journal of Ophthalmology, 2019, 55:950-952)

One case complained of amaurosis after exercise for more than 10 years, and the visual acuity of his right eye declined for 1 month. He went to the ophthalmology department. In the past, the arterial pulsation of both upper limbs disappeared. The specialist examined a large amount of vitreous hemorrhage in the right eye, and the fundus was not clear. The retina of the left eye was scattered with punctate microangiomas, neovascularization and bleeding spots. Magnetic resonance angiography and fluorescein fundus angiography were performed. He was diagnosed as vitreous hemorrhage in the right eye, ischemic retinopathy in both eyes, retinal hole in the right eye, optic disc neovascularization in both eyes, and Takayasu arteritis. After vitrectomy in the right eye, anti-vascular endothelial growth factor therapy in both eyes, retinal laser photocoagulation, the ocular and general conditions were significantly improved after medical treatment of Takayasu arteritis.(Chinese Journal of Ophthalmology, 2019, 55:953-955)

Liu Guoguo, second-level professor (chief physician), director of the Institute of Ophthalmology of Xiamen University, director of the Department of Ophthalmology of Xiang' an Hospital affiliated to Xiamen University; Distinguished Professor of "Changjiang Scholars Award Program" of Ministry of Education, winner of National Outstanding Young Scholars Fund, Chief Scientist of National "863" Key Project; Standing Committee Member of Ophthalmology Branch of Chinese Medical Association, Standing Committee Member of Ophthalmologist Professional Committee of Chinese Medical Doctors Association, Chairman of Ophthalmology Professional Committee of Cross-Strait Medical and Health Exchange Association and Leader of Ocular Surface and Tear Diseases Group, Deputy Editor-in-Chief of Chinese Journal of Ophthalmology; Academician of Asia Pacific Academy of Ophthalmology, President of Asian Dry Eye Society, Member of Asian Keratology Society.

The patient was a 72-year-old male. Because of blurred vision in his left eye for 7 years and swelling and pain for more than 2 months, he went to the Department of Ophthalmology, Daping Hospital, Army Medical University. Previous history of hyperlipidemia; I lost my left eye 6 years ago. Stenosis of the left carotid artery and plaque formation were found in the local hospital. Diagnosis: left eye ocular ischemia syndrome. Eye examination: the visual acuity was 0.6 in the right eye and no light sensation in the left eye; IOP was 13 mmHg (1 mmHg =0.133 kPa) in the right eye and 47 mmHg in the left eye; The lens of the right eye was slightly opaque, and no abnormalities were found in the fundus; See anterior segment of left eyeQuintessence Picture 1She could not see clearly. Diagnosis: Neovascular glaucoma in left eye; Cataract in the left eye.

Herpes simplex virus (HSV) infection can cause inflammatory reactions and angiogenesis of the cornea, which significantly reduce corneal transparency. Herpes stromal keratitis (HSK) is an immune mediated disease caused by HSV infection, and is associated with inflammation and angiogenesis of the cornea. It is difficult to control HSK therapeutically. Repeated episodes of HSK can result in chronic inflammatory disease in the corneal stroma. Neovascularization plays a key role in the pathogenesis of HSK, so inhibiting the angiogenesis will help to control HSK disease. In this review, the pathomechanism of HSK is described. The roles of multiple cytokines and soluble mediators in corneal vascularization are discussed, and the potential ways of preventing and controlling corneal vascularization induced by HSK are summarized. (Chin J Ophthalmol, 2019, 55:956-960)