Volume 52 · Issue 03 · 2016

The academic report in this issue focuses on advances in ocular surface diseases. The responsible editorial committee responsible for the planning, composition and review of the key contents of this issue is Professor Shi Weiyun.

Corneal disease ranks second among blinding diseases in China, with the corneal blindness taking up one fourth of the blind population. It has a high incidence and a low rate of sight rehabilitation. The lack of cornea donors and the shortage of corneal specialists have become the bottleneck that hampers the development in curing corneal disease. It is of primal importance to find sufficient donor sources in order to alleviate the current situation. In 2015, the world's first artificial bioengineered cornea was approved by CFDA to be applied clinically as a substitute for human cornea in lamellar keratoplasty. It will not only relieve the cornea donor shortage, but will also spur the training and practices of corneal specialists. The application and clinical trials of such an innovative product will significantly boost fundamental and clinical researches in corneal disease in our country, helping more patients with corneal blindness to recover their sights.(Chin J Ophthalmol, 2016, 52: 161-163)

Uveitis is a common eye disease worldwide, with many causes and types. The classification methods include etiology classification, anatomical location classification, clinicopathological characteristics classification, disease course classification, etc. According to the anatomical position, uveitis can be classified into four categories: anterior uveitis, intermediate uveitis, posterior uveitis and panuveitis. Anterior uveitis is the most common type of uveitis, accounting for approximately 50% of the total number of patients. According to the course of the disease, uveitis can be divided into three types: acute, chronic and recurrent. Natural course of acute anterior uveitis<3 months, natural course of chronic anterior uveitis>3 months^[1]。

catalogue

To summarize the clinical characteristics, diagnosis, and treatment of blepharokeratoconjunctivitis (BKC).

Retrospective analysis. One hundred and seventy-two patients were diagnosed as BKC between January 2012 and December 2014 at Beijing Tongren Hospital. The clinical characteristics, the degrees of blepharitis and BKC, and the therapeutic effect were evaluated.

The patients were aged from 2 to 78 years (mean, 27±18 years). Forty-nine patients (28.5%) were males, and 123 patients (71.5%) were females. One hundred and five patients had photograph records of lid margin, cornea, and conjunctiva. BKC was unilateral in 28 (26.7%) of them, and bilateral in 68 (64.8%) with similar degrees and in 9 (8.6%) with different degrees. The disease was mild in 39 patients (40.6%), moderate in 24 patients (25.0%), and severe in 33 patients (34.4%). There was no significant difference in the degree of BKC between males and females (χ²=1.022, P=0.600). A total of 1 875 patients were diagnosed as blepharitis during the same period, and 172 patients (9.2%) were complicated by BKC. Female patients with blepharitis were more susceptible to BKC (χ²=8.355, P<0.05). Among the children patients with blepharitis, the incidence of BKC was significantly higher than that in the other groups (χ²=224.566, P< 0.05), but in the degree of BKC, there was no significant difference among groups. Typical clinical findings consisted of punctuate epithelial and subepithelial haze, stromal infiltrates, corneal ulcer, corneal scar, and corneal pannus. The patients were followed up for 1 to 80 months (mean, 7 months). According to the different degrees of BKC, the patients were given treatment for 1 month. Sixty-nine patients (71.9%) had clinical recovery, and the other cases were improved obviously. Nine patients (15 eyes) had recurred BKC during the follow-up period, and the recurrence rate was 9.2%.

BKC is not uncommon in patients suffering blepharitis, with a variety of clinical characteristics. Female and children patients with blepharitis are more susceptible to BKC. It is vital to perform standardized diagnosis and treatment for improvement of therapeutic effect. (Chin J Ophthalmol, 2016, 52:174-179)

To evaluate the preliminary results of femtosecond laser-assisted Descemet stripping endothelial keratoplasty (FS-DSEK) for the treatment of bullous keratopathy.

In the nonrandomized, prospective, consecutive case series, 7 eyes with bullous keratopathy induced by cataract surgery received FS-DSEK surgery between September and December 2013. Standard Descemet stripping endothelial keratoplasty procedure was performed. The Descemet membrane and abnormal endothelial layer were stripped from the central recipient posterior surface in a diameter of 7.75 mm. The graft was fixed to the edge of recipient cornea with one single stitch. The donor lenticule was produced by Intralase 150 femtosecond laser with a diameter of 7.75 mm. The adherence of donor lenticule to the recipient posterior stroma and postoperative donor lenticule dislocation were monitored in the early stage after surgery. Best spectacle-corrected visual acuity, refraction, endothelial cell density and thickness of grafts were measured preoperatively, and at 1 week, 1, 3, 6 and 12 months after FS-DSEK.

Two eyes had graft dislocation, with a gap between the graft and recipent posterior stroma at 2 days after surgery. The grafts were repositioned after bubbles were added into the anterior chamber. All grafts were well adherent to the recipent posterior stromal surface at 1 week postoperatively. One graft failed at 3 months postoperatively, and penetrating keratoplasty was performed. At 12 months, the best spectacle-corrected visual acuity was 0.04 to 0.7, the mean endothelial cell density was (1 698.0±251.8) cells/mm², and the mean thickness of grafts was (124.2 ± 11.4) μm.

Femtosecond laser-assisted Descemet stripping endothelial keratoplasty was effective in treating bullous keratopathy. Stitching the graft to the recipent cornea can prevent postoperative graft dislocation effectively. (Chin J Ophthalmol, 2016, 52:180-185)

To evaluate the practical value of AutoCAD in quantitative analysis of corneal subbasal epithelial nerves with different degrees of dry eye.

Ninety patients were divided into groups of mild, moderate, and severe dry eye, 30 patients (60 eyes) in each group. And 30 healthy volunteers were recruited as the normal control group. Confocal microscopy was used to observe the length of the subbasal epithelial nerve plexus. The images were analyzed by AutoCAD software to determine the density (mm/mm²), the number of branches, and the curvature score of the subbasal epithelial nerves. These data of patients with dry eye and the controls were statistically compared, by analysis of variance(ANOV).

By AutoCAD software, quantitative analysis of the corneal subbasal epithelial nerves was successfully performed. The nerve density in the patients with mild dry eye[(16.70±3.43) mm/mm²] was not significantly different from the controls[(15.87 ± 2.75) mm/mm²] (P=0.880), but the number of nerval branches 13.43±2.46 and the curvature 3.10±0.80 increased significantly (P<0.001). The nerve density in the patients with moderate and severe dry eye was significantly different from that in the normal control group (F=114.739,P<0.001). The neural density was significantly lower in the patients with severe dry eye than the controls, but there was no significant difference in the curvature scores between the two groups (P= 0.557).

AutoCAD software is useful in the quantitative analysis of corneal nerve images under a confocal microscope. The corneal subbasal epithelial nerve density, the number of branches, and the curvature of the nerves are related to the degree of dry eye, and may be used as clinical indicators. (Chin J Ophthalmol, 2016, 52:186-191)

To complete a preliminary evaluation of the feasibility of implanting the complex of mouse bone marrow mesenchymal stem cells (BMSC) and a tissue engineering scaffold into rabbit corneal lamellae, based on which a solution may be proposed to consolidate the keratoprosthesis and the recipient surface, and to reduce the risk of complications.

This experimental study was composed of two parts. (1) In vitro: some mouse BMSC were marked with red fluorescent proteins (RFP) and integrated with a decellularized pig articular cartilage extracellular matrix (ECM) scaffold. The cell survival was observed under a fluorescence microscope at 4 and 8 weeks. The cell distribution was examined by toluidine blue staining. The pore structure and the cell adhesion were observed under a scanning electron microscope. (2) in vivo: the complex of mouse BMSC and a decellularized scaffold was implanted into the lamellar cornea of 8 rabbit eyes with the fellow eyes as the controls. The eyes were sampled for observation using HE staining under a light microscope at 2, 4 and 8 weeks, respectively. The cell survival was examined under a fluorescence microscope, and the intracorneal cell survival at 8 weeks was observed using in vivo imaging. The conditions of ocular anterior segment of all the experimental animals were recorded.

(1) Under the scanning electron microscope, the ECM scaffolds showed satisfactory porosity required for the adhesion and growth of cells and tissues, and the cell distribution over the cell-scaffold complex can be observed by toluidine blue staining. (2) Under the immunofluorescence microscope, cell proliferation was observed in vitro and in the interlamellar space (the maximum observation time was 8 weeks) after the RFP-marked mouse BMSC were integrated in vitro with ECM scaffolds. (3) Under the light microscope (HE staining), the stromal cells were detected to increase at each timepoint. A small number of monocytes and some mouse BMSC were observed in the superficial layer of corneal stroma, with sparsely and orderly arranged collagenous fibers and no neovascularization. All the epithelial cells appeared as mononuclear, columnar and undamaged, and the shape of ECM scaffolds, which were fused with the collagens, became unclear. (4) By in vivo imaging, it was found that the mouse BMSC survived for 8 weeks after being integrated with scaffolds and implanted into the interlamellar space of rabbit cornea. (5) After the implantation of cell-scaffold complex, severe postoperative inflammatory reactions, obvious conjunctival congestion and neovascularization were not observed. The corneal tissues surrounding the recipient area were transparent. One week later, mild inflammatory reactions were barely observed, and the cornea was transparent enough to observe the scaffold in the stromal layers. Four weeks later, the scaffolds became thinner. Eight weeks later, the scaffolds became extremely thin with normal vascular system in the corneal limbus.

The ECM scaffold is a solid and biocompatible carrier for the growth and proliferation of BMSC. The mouse BMSC can grow and proliferate in the microenvironment of the interlamellar space of cornea. (Chin J Ophthalmol, 2016, 52:192-197)

To investigate the clinical efficacy, safety, predictability, corneal sensitivity, tear function and recovery of subbasal nerves after femtosecond lenticule extraction (FLEx) and laser in situ keratomileusis (LASIK).

In this prospective, nonrandomized, comparative clinical study, 49 patients (98 eyes) were divided into two groups. FLEx was performed to treat myopia by Visumax femtosecond laser system, and LASIK was performed by Allegretto Wave laser system. The patients were followed up for 6 months. Visual acuity, manifest refraction, intraocular pressure, slit-lamp examination, corneal topography by Pentacam, tear break-up time, Schirmer test, corneal sensitivity and confocal microscopy were assessed.

Forty-four patients (88 eyes) completed the 6-month follow-up. Best corrected visual acuity (BCVA) was 0.89±0.14 in eyes with FLEx and 0.98±0.08 in eyes with LASIK at 1 day after surgery. After 10 days, BCVA was 0.98±0.09 and 1.02±0.09, respectively. At the final follow-up visit, the efficacy index was 1.09 in the FLEx group and 1.07 in the LASIK group, and the safety index was 1.12 and 1.07, respectively, in the two groups. Mean Schirmer score was (16.92±7.58) mm and (15.03±5.89) mm (t=1.316, P=0.192), mean tear break-up time was (8.94±2.57) s and (8.00±2.39) s (t=1.759, P=0.082), and corneal sensitivity was (56.46±4.49) mm and (51.38±8.16) mm (t=1.316, P=0.001) in the groups of FLEx and LASIK, respectively. At 10 days after surgery, the number of subbasal nerves was significantly decreased in the FLEx group, and in the LASIK group the subbasal nerve fibers were hardly observed. At 6 months, regenerated nerve fibers were evident in the subbasal area, which recovered faster in eyes with FLEx than in those with LASIK.

Femtosecond lenticule extraction appears to be efficient, safe and predictable for myopia. FLEx surgery is superior over LASIK in less reduction of corneal sensation and lower risk of harm to the subbasal nerve fibers. (Chin J Ophthalmol, 2016, 52:198-205)

To study the primary role of TSLPR/STAT5 signaling in inflammatory responses triggered by Aspergillus fumigatus(AF) in telomerase-immortalized human stromal fibroblasts (THSF).

Experimental study. Baseline expression of TSLPR in THSF was assessed by immunofluorescence analysis. Human recombinant TSLP was added. At 5, 15, 30 and 60 min after incubation, cells were harvested for Western blot to assess the protein levels of p-STAT5 and STAT5. After stimulated with AF hyphae for 1, 3, 6, 12, 24 and 48 h, cells were collected for measurement of mRNA of TSLPR and IL-7Rα. After incubated with AF hyphae for 12, 24 and 48 h, cells were harvested for Western blot to assess the protein levels of TSLPR, p-STAT5 and STAT5. Incubation with anti-TSLPR antibody was performed for 4 h, and at 24 h after AF hyphae were added, cells were harvested to assess the protein levels of p-STAT5 and STAT5.

Immunofluorescence staining evidenced that expression of TSLPR was visualized in THSF. Western blot assay showed that p-STAT5 protein was increased and peaked at 30 min after stimulation with hTSLP (AF group: 8.87±0.75; control group: 1.00±0.14; P<0.01). RT-PCR revealed that the expression levels of TSLPR mRNA were increased after incubation with AF hyphae for 3, 6, 12 and 24 h (AF group: 0.000 50±0.000 07, 0.001 20±0.000 11, 0.002 30±0.000 25 and 0.001 70±0.000 17; control group: 0.000 20±0.000 03, 0.000 20±0.000 05, 0.000 20±0.000 03 and 0.000 20±0.000 04; t=-9.955, -17.329, -16.735 and -18.214,P<0.01), but the expression levels of IL-7Rα mRNA were not increased significantly (t=-0.684,-0.029,-0.319,-1.034, P>0.05). In comparison with the control group, after being challenged with AF hyphae for 24 h, both TSLPR and p-STAT5 protein were increased significantly (p-STAT5: 9.46±2.08 vs. 1.00±0.06; TSLPR: 1.80±0.27 vs. 1.00±0.34; t=-7.055, -3.170,P<0.01). Western blot showed that the elevated p-STAT5 expression levels observed after AF hyphae stimulation can be inhibited by TSLPR antibody (anti-TSLPR-AF: 0.55 ± 0.20; CTR Ab-AF: 1.00 ± 0.08; t=3.506,P<0.05).

TSLP/TSLPR/STAT5 signaling pathway plays an important role in inflammatory responses triggered by AF in THSF. (Chin J Ophthalmol, 2016, 52:206-211)

To determine the prevalence of trachoma in urban and rural area in China. To provide the data evidence for the strategies of eliminating trachoma in China.

Survey was conducted in 13 suspect trachoma high prevalence provinces according to the World Health Organization trachoma grading system and Trachoma Rapid Assessment(TRA).

From 2004 to 2007, a total number of examined children which were younger than 10 years old was 59 630. The prevalence of TF was 0.94%. To sum up the data of 2004 and 2005, the prevalence of active trachoma was 1.71% for children.TT and CO was not reported. The results for subjects older than 50 years old showed that the prevalence of TT was 0.34%. We examined 26 857 adults in both 2004 and 2005.The prevalence of TF, TI, TS and CO was 0.03%,0.08%,0.88% and 0.05% respectively.

The prevalence of active trachoma of younger children was under 5%. However,the prevalence of TT of the adults was not reached the target. (Chin J Ophthalmol, 2016, 52:212-215)

The patient was a 17-year-old female. Due to the finding of yellow-white papules on both eyelids for more than 5 years, which increased progressively without obvious discomfort, I went to Beijing Tongren Hospital on May 2, 2014. Eye condition: visual acuity in both eyes 1.0, beaded yellow-white translucent papules at the root of eyelashes in both eyes (Figure 1), without eyelash loss, no flushing on the skin of both eyelids, no scales attached, no conjunctiva congestion, transparent cornea, and no abnormalities in the remaining eye signs. Follow-up medical history: The patient developed normally, had no nervous system obstacles, had hoarseness 1 year after birth, and the skin was easily injured by slight external force, which was difficult to heal. After healing, atrophic scars were left, and flaky atrophic scars were visible on the skin of the face, back, upper arm and buttocks. The parents are not intimate married and have no similar disease. Laboratory tests: blood, urine routine, liver and kidney function, blood lipids and blood sugar were all in the normal range; Chest X-ray and electrocardiogram showed no abnormalities. Otolaryngologic consultation to diagnose chronic inflammation of the vocal cords. Dermatology consultation, back skin scar was taken for pathological examination, periodic acid Schiff staining (PAS) staining was strong positive, and red transparent substance was thickened (Figure 2)。 Diagnosis: lipoid proteinosis. Treatment: Ophthalmology does not intervene temporarily, close follow-up, and there is no effective treatment in the whole body.

A 76-year-old male patient was admitted to the Department of Ophthalmology of Yantai Yuhuangding Hospital affiliated to Qingdao University School of Medicine on August 28, 2013 with rhegmatogenous retinal detachment in his right eye and high myopia in both eyes due to 5-day occlusion in his right eye. He had been highly myopic in both eyes for more than 50 years, and his left eye was blind for 12 years due to retinal detachment. Ophthalmological examination: right eye visual acuity several fingers in front of the eye, left eye no light sensation, mild vitreous opacity, horseshoe-shaped hole about 1 PD after the equator in the superior temporal quadrant of the right fundus, temporal and inferior retina detachment, involving the macula. The patient completed the preoperative examination and underwent right eye vitrectomy on August 30, 2013. During the operation, 2.5 ml of 2% lidocaine and 0.75% ropivacaine mixture were drawn with a disposable No. 5 retrobulbar injection needle (Shandong Kaili Medical Devices Co., Ltd.) and performed retrobulbar block anesthesia. The patient had no abnormal reaction. When the surgeon adjusted the microscope to the surgical field, it was found that the cornea was transparent and the intraocular pressure was not high, but the fundus showed diffuse red reflection. It was suspected that the ball wall damaged the vitreous body and was fresh, so the surgical process was immediately accelerated. Under the intraocular light guide illumination, the whole posterior pole anterior retinal vitreous body was fresh bleeding. After clearing the accumulated blood, it was found that the left eye papilla was oblique ball wall lacerated below the nose, which was about 3 PD long. The morphology and movement of retinal blood vessels were normal, and no abnormalities such as macular edema were found. The surgical process was smooth, and the corrected visual acuity of the right eye was 0.15 when discharged. The patient successfully performed silicone oil removal combined with phacoemulsification and intraocular lens implantation in the right eye on 19 December 2013. The postoperative naked eye visual acuity was 0.15, and no abnormalities were found after 3 months postoperative review (Figure 1）。

The patient was a 49-year-old male. He went to the Department of Ophthalmology of Beijing Tongren Hospital because of dry eyes. Eye examination: both eyelid margins are normal, conjunctiva is not congested, and tear river is narrow; The cornea of the left eye is small round and turbid, with negative staining. It is a white ring composed of small dot-like white particles under the corneal epithelium. Scattered white particles of different sizes can also be seen in the white ring (Quintessence Picture 1）。 The cornea of the right eye is transparent. Clinical diagnosis: Left eye Coats corneal white ring.

The patient was a 72-year-old male. Because the tumor on the nasal side of his right eye grew for 72 years and increased for 1 month, he went to Tianjin Eye Hospital. Since childhood, the patient has seen a black mass the size of a sesame seed in the canthus of his right eye, and has no symptoms such as red eyes, eye pain and vision loss, and has not been diagnosed and treated. 20 years of previous history of hypertension and 6 years after left carotid stenting. General physical examination: No obvious abnormalities were found. Eye examination: visual acuity was 0.3 for the right eye and 0.1 for the left eye; IOP was 12 mmHg (1 mmHg =0.133 kPa) in the right eye and 13 mmHg in the left eye; The eyeballs of both eyes can move freely in all directions; The appearance of the right eye is normal, and the eyelid is not red or swollen; There was no congestion in the conjunctiva, and a round-like mass with a diameter of about 7 mm was seen in the medial canthus conjunctiva, protruding about 5 mm from the surface of the conjunctiva. It was purple-black, soft in texture, clearly defined, with a small amount of bleeding when touched, and the mobility was acceptable (Essence Picture 1A), a black round lesion of approximately 3 mm in diameter was visible at the edge of the upper tarsal plate, and the surrounding conjunctiva was pigmented (Quintessence Picture 1B), a black strip can be seen under the conjunctiva of the inferior fornix, which is connected to the nasal tumor, and the surrounding conjunctiva is pigmented; There is no yellowing stain in the sclera, transparent cornea, normal anterior chamber depth, no aqueous humor flash, clear iris texture, round pupil, about 3 mm in diameter, sensitive to light, opacity of the lens, and invisibility of the vitreous body and fundus. There were no abnormalities in the appearance and anterior segment of the left eye. The lens was opaque, and the vitreous body and fundus of the eye were not clear. He was admitted to the hospital for resection of the right preorbital mass and conjunctival sac plasty. Immunohistochemical examination of resected tissues: S-100 (+ +), melanoma-associated antigen HMB45 (+ +), Ki-67>10% (Quintessence Picture 2）。 Postoperative histopathological diagnosis: conjunctival melanoma of right eye (malignant transformation of conjunctival nevus)

The patient was a 38-year-old male. Because of the decrease of visual acuity in both eyes for more than 15 years, he went to Huaibei Aier Eye Hospital. Eye examination: visual acuity in both eyes was 30 cm manual; The conjunctiva of the right eye is ciliary congested, the conjunctival epithelium is slightly dry, the corneal epithelium is rough, covered with gray-white scab-like membrane, and pannus can be seen around it; Trichiasis in the left eye, dry conjunctiva in the lateral canthus and below, loss of mucosal morphology and function, completely cutaneous, conjunctival blood vessels still visible in the medial canthus, corneal epithelium loss of transparency, cutaneous, granular appearance, invisible structure in both eyes (Quintessence Picture 1）。 Clinical diagnosis: extremely severe keratoconjunctivitis sicca in both eyes.

The corneal allograft rejection is the primary reason for graft failure, but the existing agents are of limited efficacy and may be accompanied by unacceptable morbidity. Recently, antibody-based agents have received great attention and have become an important part of therapeutic intervention for organ transplantation, which is also a research focus in the field of corneal transplantation. This review summarizes the history, current situation and mechanism of antibody-based agents in corneal transplantation. (Chin J Ophthalmol, 2016, 52: 221-225)

In clinical practice, dry eye disease (DED) is recognized as one of the most frequent reasons for chronic ocular surface disorder, which can cause the damage to the ocular surface and some symptoms associated with ocular discomfort and impaired visual quality. This common ocular problem is characterized by high incidence and difficulty in treatment. DED can make the visual disturbance and degrade the quality of everyday life and social activities in different levels. Some patients with DED often report psychological changes because of the symptoms of ocular discomfort. This article mainly summarizes the characteristics and mechanism of psychological disorder in patients with DED. (Chin J Ophthalmol, 2016, 52: 226-230)

In eukaryotic cells, the most secreted proteins and membrane proteins are compounded, modified and folded into the correct structure in the endoplasmic reticulum. Only correctly folded proteins can be transported to the golgi apparatus for further processing. If the endoplasmic reticulum is insufficient to deal with the accumulation of unfolded or misfolded proteins, balance will be broken, and endoplasmic reticulum stress (ERS) will be started. To eliminate the unfolded proteins, cells will activate unfolded protein response (UPR) immediately for self-protection. If the induced ERS is strong or persistent, the UPR could not maintain the balance of homeostasis in endoplasmic reticulum. Then the ERS will lead to C/EBP homologous protein activation and initiate cell apoptosis. The continuous ERS may participate in the occurrence and development of many diseases, such as neurodegenerative diseases and type 2 diabetes. In this article, the research progress of ERS and its relationship with glaucoma is reviewed. (Chin J Ophthalmol, 2016, 52: 231-235)

With the arrival of the new century, China's national strength has obviously enhanced, and the ophthalmology business has also been flourishing. During this period, the work of the Ophthalmology Society of the Chinese Medical Association (Chinese Ophthalmology Society) has achieved unprecedented rapid development, the scale of the National Ophthalmology Congress has been continuously expanded, and the academic and professional level and internationalization degree have been significantly improved. Domestic conferences of ophthalmology are often held in conjunction with international conferences of ophthalmology. It was also during this period that the Chinese Ophthalmology Society solved the problem of joining major international ophthalmology organizations, and the international status of China's ophthalmology has been significantly improved.