Volume 53 · Issue 09 · 2017

This issue focuses on the research progress of ocular surface diseases. Professor Sun Xuguang is the responsible editorial committee responsible for the planning, composition and review of the key contents of this issue.

Dry eye is the second most common ocular disease. In China, the incidence rate of dry eye has reached 21% to 30%, and dry eye patients have accounted for more than 30% of the total ophthalmology outpatients. Dry eye has become a common health problem that affects the working efficiency and life quality of Chinese people. Over the past decade, due to the rapid development of diagnostic equipments and new treatments for dry eye, dry eye has become one of the areas with greatest concerns in ophthalmology, and many eye institutions have set up their dry eye clinics. Although the diagnosis and treatment of dry eye has been improved in recent years, the awareness of dry eye in Chinese ophthalmologists is still too simple. In the diagnosis, the interrogation and basic examination are not given enough attention, and we are over-relying on equipments. Clinical examination and instrument operation also have not been standardized. This article emphasizes that we should pay attention to the interrogation, basic examination and standardization of clinical examination and equipment operation in diagnosing dry eye. The treatment regimen should be mostly refined and optimized to be individualized and comprehensive based on the causes, types and severity of dry eye. In addition, the physical and adjuvant therapy of dry eye should be given sufficient attention and applied reasonably. (Chin J Ophthalmol, 2017, 53: 641-644)

Nowadays, diabetes is quickly emerging as one of the biggest health-related catastrophes over the world. Its impact on people's quality of life has been gradually taken seriously. In the past few years, the connection linking dry eye to diabetes has been substantially confirmed by a series of studies. However, many areas remain uncertain due to the complex and diverse pathogeneses of diabetes related dry eye syndrome. Furthermore, the slow progression of dry eye symptoms easily conceals its connection with diabetes, which brings great challenges to timely diagnosis and effective interventions. This article aims at improving the clinical understanding of this kind of disease and standardizing its diagnosis and treatment by outlining the correlation between diabetes and dry eye.(Chin J Ophthalmol, 2017, 53: 645-647)

Demodex infestation is a common cause of blepharitis and now is drawing more and more attention from clinicians. Demodex mite is the most common age-related ectoparasite of human being and may be detected from asymptomatic normal population. Furthermore, the pathogenesis of demodicosis remains unclear. Therefore, the commonly accepted diagnostic criteria of demodex infestation related blepharitis have not been established. Herein, we summarize the related studies about ocular demodicosis and comment the debates about the diagnosis of the disease. We also propose diagnostic criteria of demodex blepharitis. (Chin J Ophthalmol, 2017, 53: 648-652)

Pterygium is a benign proliferative ocular surface disease characterized by hyperplasia of the bulbar conjunctiva in the palpebral fissure area and the fibrovascular tissue underlying it growing across the limbus into the cornea^[1]。 As a common ocular surface disease in China, pterygium can not only affect the appearance, but also cause eye discomfort, vision loss, eye movement disorder, etc. The pathogenesis of pterygium is currently unclear and surgery is the only effective treatment. Common clinical procedures are based on pterygium removal, combined with autologous conjunctival transplantation, limbal stem cell transplantation, amniotic membrane transplantation, etc^[2]。

meibomian gland dysfunction (MGD) is a common ocular surface disease in clinic. Due to the lack of specificity of symptoms, missed diagnosis and mistreatment often occur in clinic. Since the International MGD Research Group published a series of research reports on MGD in 2011^[1]All countries have attached great importance to the clinical diagnosis and treatment of MGD, and formulated corresponding treatment guidelines according to the disease characteristics of each country, making the diagnosis and treatment of MGD more standardized. The incidence of MGD in China is high, which is the main cause of dry eye. Long-term meibomian gland lesions will cause inflammatory reactions on the ocular surface, which will lead to corresponding changes in the cornea and conjunctiva. In severe cases, visual acuity will decrease, resulting in poor prognosis. In order to further standardize the diagnosis and treatment of MGD in China, the China Branch of Asian Dry Eye Association and the Ocular Surface and Tear Diseases Group of the Ophthalmology Committee of Cross-Strait Medical and Health Exchange Association have formulated the expert consensus on the diagnosis and graded treatment of MGD in China according to the clinical characteristics of MGD in China and the research progress at home and abroad for clinicians' reference.

To analyze the etiology and drug sensitivity of bacterial keratitis and their changes, and to provide evidence for treatment and drug selection of bacterial keratitis.

Retrospective case series study. From January 2006 to December 2015, corneal specimens suspected of bacterial infection were collected and cultured in Beijing Tongren Eye Center. General information of patients, etiological results and drug sensitivity test results were summarized and analyzed. The Chi-square test and Spearman correlation analysis were performed using SPSS 20.0 software.

A total of 6 220 corneal specimens were collected, and 1 133 of them were positive. The positive rate was 18.2%. Among the positive specimens, 673 were from males and 460 were from females, aged from 11 days to 94 years old, with an average age of (45.3±22.1) years old. Among all isolated bacteria, 741 strains of Gram-positive cocci accounted for 62.0%, and 303 strains of Gram-negative bacilli accounted for 25.2%. Three hundred and twenty-one strains of Staphylococcus epidermidis was the most common isolates, accounting for 26.9% of all bacteria isolated, which was followed by 131 Strains of Pseudomonas aeruginosa (11.0%). In vitro drug sensitivity test results of 11 antibiotics showed that the sensitivity rate of gatifloxacin was highest, while the sensitivity rate of tobramycin and ceftazidime was lower than the other drugs. Multi-drug resistant bacteria accounted for 29.2% of all bacteria isolated.

Bacterial species causing corneal infection are changing over time in northern China within recent 10 years. Staphylococcus epidermidis is the most common bacteria isolated. The sensitivity rate of corneal bacteria to the fourth generation of fluoroquinolone antibiotics represented by gatifloxacin is highest. (Chin J Ophthalmol, 2017, 53: 662-667)

To study the sensitivity and specificity of tear film objective scatter index to the diagnosis dry eye disease (DED).

A prospective case-controlled study. Fifty-three patients with DED and 32 healthy age- and sex-matched control subjects were included from July to October 2016. All subjects underwent the examinations sequentially as follows: evaluation of ocular surface disease symptoms using the Ocular Surface Disease Index, optical quality detection, lipid layer thickness, tear film breakup time and SchirmerⅠtest. With Optical Quality Analysis SystemⅡ, the values of modulation transfer function cut off, basic objective scatter index (OSI) and total OSI were measured. To eliminate the influence of other refractive media, the tear film OSI (TF-OSI) was calculated, and the difference in TF-OSI between two groups was analyzed with the independent-samples t test. Spearman's correlation analysis was used to detect the correlation of each parameter in the DED group. With the receiver operating characteristic curve and the area under the curve (AUC), the specificity and sensitivity of TF-OSI and other parameters were described to differentiate DED from normal eyes.

In the dry eye group, the value of modulation transfer function cut off (32.07±11.95) was significantly lower than the normal group (39.38±9.44, t=-3.096, P=0.003) , and the mean value and dispersion of TF-OSI (0.50±0.43, 0.52±0.81) were higher than the normal group (0.21±0.16, 0.12±0.01) (t=4.300, P=0.000, t=3.546, P=0.001) . The mean value of TF-OSI had a positive correlation with lipid layer thickness (r=0.365, P=0.007) and dispersion of TF-OSI (r=0.581, P=0.000), and a negative correlation with MTF cut off (r=-0.368, P=0.007). To the diagnostic value of DED, the mean value of TF-OSI had a sensitivity of 0.736, a specificity of 0.762, and the AUC was 0.764. The dispersion of TF-OSI had a sensitivity of 0.811 and a specificity of 0.810, and the AUC was 0.900.

In the DED group, the mean value and dispersion of TF-OSI were higher than the normal group. With its advantages, the TF-OSI may be a new method for the auxiliary diagnosis of dry eye. (Chin J Ophthalmol, 2017, 53: 668-674)

To explore short-term effect of intense pulsed light (IPL) combined with meibomian gland expression in treating meibomian gland dysfunction (MGD).

This study was a prospective, randomized, double-masked, controlled study. Forty-four MGD patients were enrolled in the study and received three consecutive IPL treatments with an interval of 4 weeks. One eye of each patient was randomly assigned as the study eye receiving the IPL therapy with an energy of 14-16 J/cm², and the fellow eye was as the control eye receiving a placebo therapy with 0 J/cm². Meibomian gland expression was immediately performed after the IPL treatment in both eyes. Efficacy was evaluated through assessment of the meibomian gland yielding secretion score (MGYSS) , SPEED questionnaire, tear film break-up time (TBUT), cornea fluorescein staining and infrared meibography. Safety was evaluated through best spectacle corrected visual acuity, intraocular pressure, slit lamp examination and fundus examination. These examinations were performed before and after each treatment.

Significant improvements were observed in the MGYSS and TBUT after IPL treatments (P<0.05). The improvements compared to the baseline of MGYSS at the upper eyelid in the treatment eyes were significantly higher than those in the control eyes after the first treatment (Z=-2.036, P=0.003). The improvements compared to baseline of MGYSS at the lower eyelid and the TBUT in the treatment eyes were significantly higher than those in the control eyes after the second treatment (Z=-2.999 and -2.036, respectively P=0.007 and 0.042, respectively). SPEED and cornea fluorescein staining were decreased in both eyes after IPL treatments, but there was no statistical difference between the two eyes. No obvious complication was observed in the study.

IPL treatment combined with meibomian gland expression is an efficient and safe therapy, and can increase meibomian gland yielding secretion, increase the TBUT, relieve the symptoms and repair the corneal epithelium defects for MGD eyes. (Chin J Ophthalmol, 2017, 53: 675-681)

To investigate the treatment effect of keratectomy combined with intrastromal injection of voriconazole on fungal keratitis.

Retrospective study. Ninety-eight fungal keratitis patients (98 eyes) were treated by keratectomy combined with intrastromal injection of voriconazole in Shandong Eye Hospital from January 2013 to May 2015. The corneal ulcers were mostly located in the paracentral or peripheral cornea, which incompletely blocked the pupil area. Slit lamp and anterior segment optical coherence tomography (AS-OCT) were used for lesion detection. The maximum lesion diameter was ≤5 mm, and the maximum depth was not more than half of the full corneal thickness. Because the anti-fungal drug treatment for 3-7 days was not effective, keratectomy was performed with intrastromal injection of voriconazole. The excision extension was 0.5 mm greater than the ulcer diameter, and keratectomy could be repeated until the infiltrative tissues were completely removed. Anti-fungal drug therapy was carried on after surgery. The wound healing and complications were observed.

All the subjects were diagnosed as fungal keratitis by corneal scraping and confocal microscopy. With an average lesion diameter of (3.72±1.23) mm, the corneal ulcers were located in the paracentral cornea in 30 patients (30.6%) and in the peripheral cornea in 68 patients (69.4%). The infiltrative depth of 74.5% of the cases detected by AS-OCT were ≤1/2 corneal thickness. The fungal keratitis in 95 cases was cured successfully. Conjunctival flap covering surgery (2 cases) and penetrating keratoplasty (1 case) were performed when the conditions were poorly controlled. Among the 95 cured cases, the ulcer healing time ranged from 3 to 19 days, and ≤7 days in more than half of the cases (48 cases). The average corneal thickness was (433.2±119.3) μm at 3 months, and the corneal endothelial cell density was (2 344.0±404.6) cells/mm ². The uncorrected visual acuity was improved in 71(74.7%) eyes, of which 3 cases had a vision of 1.0.

For fungal keratitis with a lesion diameter of<6 mm and a depth not more than half of the full corneal thickness, keratectomy combined with intrastromal injection of voriconazole could achieve ideal outcomes. The visual acuity recovered quickly, the therapy course was shortened, and the necessity of keratoplasty and other high risk surgeries was reduced.(Chin J Ophthalmol, 2017, 53: 682-688)

To observe the clinical characteristics of allergic conjunctivitis, and the correlations with skin prick test results.

A retrospective study. Forty patients with positive skin prick test result were included. Patients underwent an ophthalmologic examination to identify their primary presenting signs and symptoms. The allergy types were divided into 5 groups. All dates were analyzed for the dependence, normality and homogeneity of variance. Chi-square test, Mann-Whitney U test, Kruskal-Wallis H test and Spearman correlation analysis were performed accordingly.

Among 40 patients, 18(45.0%) had a clinical diagnosis of seasonal allergic conjunctivitis, 14(35.0%) had perennial allergic conjunctivitis, 5(12.5%) had vernal keratoconjunctivitis, and 2(5.0%) had atopic keratoconjunctivits, and 1(2.5%) had giant papillary conjunctivitis. There was no significant difference in the number of symptoms and signs score among different types of allergic conjunctivitis, the score of itching and hyperemia had a positive relationship with the number of positive allergens (r=0.74, P<0.05. r=0.96, P<0.05). The primary symptoms and signs are itching and hyperemia; dust and pollens are the most common allergens. The more positive result of the test of the allergen, the more symptoms and signs encountered in terms of severity.

Seasonal allergic conjunctivitis was the most prevalent disorder, the most important clinical characteristics of allergic conjunctivitis are itching and conjunctival congestion, the main allergens are dust and pollens, patients may be sensitive to multiple allergens. (Chin J Ophthalmol, 2017, 53: 689-693)

To evaluate the clinical results of keratoconic eyes with a thin cornea treated with accelerated transepithelial corneal collagen cross-linking (A-TE-CXL) within 1 year.

Nineteen eyes of 19 patients with progressive keratoconus with a minimum corneal thickness from 380 μm to 420 μm (including the epithelium) were included in this prospective, nonrandomized clinical study and treated with A-TE-CXL. Scoring of pain and foreign body sensation, slit lamp examination, uncorrected visual acuity, best corrected distance visual acuity, corneal topography, anterior segment optical coherence tomography, in vivo corneal confocal microscopy and endothelial cell count were assessed before surgery and at 1, 3, 6 and 12 months postoperatively. Paired t test was applied for statistical analysis.

Mild pain and moderate foreign body sensation were reported by most patients within postoperative 24 hours, but rapidly disappeared on day 2. Extremely mild epithelial damage was observed within postoperative 24 hours, and the epithelium fully recovered on day 2. Improvement of visual acuity was recorded at 3 and 12 months. Pentacam corneal topography revealed a significant reduction of the thickness of the thinnest location from(395.2±13.8)μm preoperatively to (378.9±17.1)μm at 1 month postoperatively (t=2.982, P<0.01). Front curvature values were reduced postoperatively. K_MAX was significantly decreased at 12 months (55.67±4.91) compared with (57.35±5.54) preoperatively, while K2 was also significantly decreased at 12 months (52.18±3.70) compared with (52.70±3.56) preoperatively (K_MAX, t=3.044, P<0.01. K2, t=2.384, P<0.05) . Within 1 month postoperatively, optical coherence tomography exhibited an increase of reflectance with a demarcation line in the anterior stroma. In vivo confocal microscopy also showed significant thickening and increased connections of collagen fibers with a maximal depth at about 90 to 120 μm. The corneal endothelial cell density remained stable ( t=0.692, P>0.05). None of the patients showed postoperative complications such as corneal infection, scarring and ulceration.

Within 1 year postoperatively, A-TE-CXL was effective and safe for the management of progressive keratoconus with a thin cornea. A-TE-CXL showed the advantages of very short time consuming in surgery, rapid recovery and very few complications, and had the potential to become a valid alternative for the treatment of keratoconus. (Chin J Ophthalmol, 2017, 53: 694-700)

meibomian gland dysfunction (MGD) is a chronic, diffuse abnormality of the meibomian gland, usually characterized by obstruction of the terminal duct of the meibomian gland and/or changes in the amount or substance secreted by the meibomian gland, often causing ocular irritation symptoms, abnormal tear film, inflammatory reaction and injury of the ocular surface^[1,2]。 This concept was developed by Gutgesell et al.^[3]It was first proposed in 1982 that obstruction of meibomian gland duct, which may be related to abnormal keratosis, is an important role in the pathogenesis of meibomian gland dysfunction. The main clinical manifestations are red eyes, watery eyes, burning sensation, foreign body sensation, dryness, irritation, itching, visual fatigue, visual fluctuation and other symptoms, which are very common in oily skin and the elderly, and are the main cause of excessive evaporation or lipid deficiency dry eye. In recent years, clinical studies have found that the incidence of MGD in the population is high. Foreign literature has reported that the prevalence of MGD in the European population has reached 20%, and that in the Asian population has exceeded 60%^[4,5]。 At present, the related research of MGD has become one of the hot spots of ophthalmology research.

Blepharokeratoconjunctivitis (BKC) refers to a series of conjunctival and corneal lesions secondary to Blepharokeratoconjunctivitis, mainly including: alveolar keratoconjunctivitis, corneal punctate erosion, punctate keratitis, marginal keratitis, corneal ulcer and corneal neovascularization^[1]。 The author clinically applied intense pulsed light (IPL) to treat 3 cases of BKC, which are reported as follows.

fungal keratitis (FK) is a severe blinding eye disease caused by fungal infection^[1]。 Especially in underdeveloped countries such as Asia and Africa, it is the main eye disease causing blindness. In recent years, its incidence has increased year by year, and it has ranked second among infectious keratitis^[2]The pathogenic bacteria of this disease are highly resistant to drugs, and the treatment is quite difficult. Therefore, it has been paid more and more attention by clinicians. According to the statistics, there are more than 70 pathogenic bacteria that can cause FK^[3]However, the pathogenic strains isolated in clinical practice are mainly concentrated in a few species. According to literature reports, the main pathogenic species of FK in northern China are Fusarium, Aspergillus and Alternaria^[4,5]。 In clinical practice, fungal keratitis caused by Zygomycetes is very rare, and the reported in this paper is one of the species of Zygomycetes, and there are few reports of keratitis caused by it in Chinese literature. This article focuses on the clinical manifestations, treatment methods and biological characteristics of the bacteria, in order to help the early diagnosis and treatment of the mycous keratitis.

Child female, 2 years old, fraternal twins, 34⁺²Weekly cesarean section, because right eye mass found from birth admitted to hospital. There was no family history, parents had no history of intimate marriage, mother took levothyroxine sodium tablets during pregnancy, no history of taking other drugs, no history of toxic substances, radiation exposure, no history of infection, no pregnancy complications such as hypertensive disorder during pregnancy and diabetes during pregnancy. The fraternal twin brother of the child suffered from neonatal necrotizing enterocolitis and underwent surgical treatment. He recovered well after operation, and no abnormalities were found. Physical examination: suffering from right external auditory canal atresia (Figure 1), which is microtia with short ipsilateral face (Figure 2,Figure 3), a yellowish-white mass of the cornea and conjunctiva in the inferior temporal area of the right eye, about 7.0 mm in diameter, invading the cornea about 3.5 mm, with clear borders and visible hairs (Figure 4）。 Auxiliary examination: Cardiac ultrasound showed dextrocardiac rotation, coronary sinus dilatation, and persistent left superior space. The thoracic orthogonal position shows multiple deformities of the spine (Figure 5）。 MRI of the head showed no obvious abnormality, and the developmental quotient was normal. Admission diagnosis: Goldenhar syndrome. After admission, the right eye corneal dermoid tumor resection and lamellar keratoplasty were performed under general anesthesia. Postoperative pathological report: Dermoid tissue, surface lined with squamous epithelium, hair follicle structure in subcutaneous fibrous tissue (Figure 6)。 Tobramycin and dexamethasone eye ointment were given to the eyes after surgery, 3 times/d for 1 week, 2 times/d for 1 week, and 1 time/d for 1 week for 3 weeks. The corneal graft was reexamined 7 days after surgery and the suture was removed 1 month after surgery. Retrospective 3 months after surgery: corneal graft was transparent in place (Figure 7，Figure 8）。

The patient was a 63-year-old male. Because of blurred vision in his right eye for 2 years, he went to the Department of Ophthalmology, Affiliated Hospital of Jining Medical College. No previous systemic diseases such as hypertension and diabetes. Eye examination: visual acuity was 0.15 for the right eye and 0.6 for the left eye; IOP was 16 mmHg (1 mmHg =0.133 kPa) in the right eye and 15 mmHg in the left eye; The corneas in both eyes are transparent, the pupil diameter is approximately 2.5 mm, and it is sensitive to light, with mild opacity of the lens in the left eye and fan-shaped opacity of the lens in the right eye (Quintessence Picture 1）。 Clinical diagnosis: Age-related cataract in both eyes (opacity of the fan lens in the right eye).

Endothelial keratoplasty (EK) has gradually replaced penetrating keratoplasty (PKP) and has become the main method for the treatment of endothelial dysfunction in developed countries in recent years. EK is safe and effective and can achieve good postoperative vision. The surgical techniques and postoperative effects have been improved continuously along with the development of microsurgical technology and surgical instruments. The EK surgeries mainly include Descemet stripping endothelial keratoplasty (DSEK), Descemet stripping automated endothelial keratoplasty (DSAEK), Descemet membrane endothelial keratoplasty (DMEK) and ultra-thin Descemet stripping automated endothelial keratoplasty (UT-DSAEK), which have different characteristics and advantages compared with PKP. In this article, the characteristics of different EK surgeries, postoperative effects and related complications in clinical research are reviewed. (Chin J Ophthalmol, 2017, 53: 714-720)