Volume 52 · Issue 09 · 2016

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

Corneal transplantation is an important method in the treatment of corneal blindness. It is imperative to improve the treatment effectiveness of corneal disease and reduce the possibility of corneal blindness with the progress of corneal transplantation surgery, the construction and development of eye banks and the rational use of donor materials. This article reviews the component corneal transplantation technology promotion, eye bank construction and preparation of donor slices for component corneal transplantation surgery. (Chin J Ophthalmol, 2016, 52: 641-643)

Corneal epithelial injury refers to the pathological state in which the function and integrity of corneal epithelial barrier are destroyed due to various factors, resulting in partial or full loss of corneal epithelial cell layer. Clinically, it can be manifested as diffuse punctate loss or erosion of corneal epithelium, repeated exfoliation and defect of corneal epithelium, accompanied by different degrees of ocular surface inflammatory reaction, and in severe cases, it can lead to corneal stromal disease and affect visual function.

To observe the morphology, fibrosis grade and inflammatory infiltration of meibomian glands using in vivo confocal microscopy(IVCM)in meibomian gland dysfunction(MGD)patients.

A prospective case-controlled study. According to the diagnostic criteria of MGD, 20 MGD patients(20 eyes)were included in our study from August to October 2015. Fifteen normal subjects(15 eyes)were also studied. Methods All subjects completed the questionnaire of the Ocular Surface Disease Index(OSDI), lid margin and ocular surface examination by slit lamp microscropy, tear film break-up time(TBUT)test, corneal and conjunctival staining(Oxford scale), Schirmer I test, infrared meibomian photography and IVCM. Main outcomes in IVCM included meibomian gland acinar longest diameter(MGALD), meibomian gland acinar shortest diameter(MGASD), meibomian gland acinar unit density(MGAUD), meibomian gland acinar unit area(MGAUA), meibomian gland inflammatory cell density and fibrosis degree. The parameters between the MGD group and the control group were compared using the independent samples t test.

The OSDI score[(31.80±22.97)points], 1id margin abnormality score[(3.10±0.31)points], loss rate of meibomian glands(38.31%±19.94%)and corneal and conjunctival staining score[1.00(2.75)points]in the MGD group were obviously higher than those in the control group[(7.93±6.51)points,(0.33±0.31)points, 21.31% ± 7.70%, and 0.00(1.00)points,P=0.001, P<0.001,P=0.004, and P=0.037, respectively]. The TBUT was significantly lower in the MGD group[(3.35±2.28)s]than in the control group[(6.67±2.51)s,P<0.001]. According to Schirmer I test, there was no significant difference in the two groups(P=0.139). The mean values of MGALD[(156.80 ± 46.10)μm], MGASD[(38.75 ± 11 .72)μm], MGAUA[(10 113.84 ± 5 531.21)μm²], meibomian gland inflammatory cell density[(621.90 ± 405.63)cells/mm²]and fibrosis degree 1.50(1.00)in the MGD patients were larger than those in the control group[(67.47 ± 9.117)μm,(22.00 ± 2.95)μm,(3 102.13 ± 1111.97)μm²,(188.80 ± 72.25)cells/mm², and 0.00(0.00), all P<0.001, respectively]. The mean MGAUD was lower in the MGD patients[(61.10 ± 34.97)glands/mm²]than in the control group[(105.07±18.58)glands/mm², P<0.001].

IVCM was pertinent to investigate the meibomian glands by detecting the irregularity of meibomian orifices, the diameter and area, and the inflammation and fibrosis levels in MGD patients. It may have a potential clinical value for the diagnosis of MGD. (Chin J Ophthalmol, 2016, 52: 649-656)

To evaluate the efficacy of topical voriconazole in patients with fungal keratitis caused by different fungal species.

Interventional case series. Eighty-four patients aged 18 years or older from central China with confirmed fungal keratitis who presented at the outpatient department of Henan Eye Institute were enrolled in the study. The patients underwent in vivo confocal scanning laser microscopy examination, coneal scraping and microscopic examination and fungal culture, and then received topical voriconazole, closed curative effects were conducted. The sensitivity of three different diagnostic techniques, spectrum of the fungi, cure rate for fungal corneal infection related to each species were analyzed.

In our study, 84 patients were diagnosed with fungal keratitis based on clinical symptoms, and results of at least one of the examinations of in vivo confocal scanning laser microscopy, conventional smear, and corneal scraping culture and the sensitivity were 92.85%(78/84), 85.71%(72/84), 84.52%(71/84)respectively. In viro confocal scanning laser microscopy. Successful management was achieved in 83.33% of the patients. Topical voriconazole treatment failed in 14 patients(16.67%), who required surgical treatment. In 36 patients with Fusarium corneal infections, 26(72.22%)were successfully treated with topical voriconazole; however, in 18 patients with Aspergillus corneal infections and 7 patients with Alternaria corneal infections, 94.44% and 100.00% of them were successfully treated, respectively. In a case-based dynamic tracking study, in vivo confocal microscopy provided real-time dynamic detection of surviving hyphae. The existence of hyphae was(38.35±17.32)days for Fusarium,(25.00±16.11)days for Aspergillus,(21.00±4.36)days for Alternaria, and(41.50±31.68)days for the focus in the deep stroma. The duration of treatment was similar for all four groups.

Topical application of voriconazole is on effective method for the freatment of fungal keratitis Topical voriconazole is highly effective for fungal keratitis caused by Alternaria spp. and Aspergillus, however, for Fusarium, it is relatively low effective. (Chin J Ophthalmol, 2016, 52: 657-662)

To study the clinical outcome of autologous ipsilateral lamellar corneal-flap transposition for treatment of peripheral corneal perforation.

Medical records of 13 patients who underwent autologous ipsilateral lamellar corneal-flap transposition for peripheral corneal perforation from January 2008 to February 2015 were retrospectively reviewed. The diameter of the corneal ulcers was all ≤ 3.0 mm, and the diameter of perforations was all ≤ 2.0 mm. All patients were followed up for 3-12 months with an average of 8 months. The healing of ulcer, clarity of the grafts, pre-and postoperative visual acuity, and astigmatism were documented and analyzed.

At 1 day after surgery, all patients had normal anterior chamber depth without aqueous leak. No double chamber or iris synechia was found. The corneal grafts showed mild to moderate edema. On postoperative days 7-14, the corneal edema receded, the grafts became transparent gradually, and the ulcer margin was blurred. Three months after surgery, all the grafts remained transparent. There was no recurrence of ulcer during the follow-up period. The best corrected visual acuity before and after surgery was 0.44 ± 0.19 and 0.47 ± 0.20, respectively, which indicated no statistically significant difference(t=0.706, P=0.461). The corneal astigmatism before and after surgery was 0.44±0.19 and 0.47±0.20, respectively, which showed statistically significant difference(t=2.391, P<0.05).

Autologous ipsilateral lamellar corneal-flap transposition is a safe and effective surgical procedure for treating peripheral corneal perforation. It can be considered as an alternative method for penetrating or lamellar keratoplaty when the availability of corneal tissue is limited, or for cases with a high risk of developing immunologic allograft rejection, although the surgical indications are limited. (Chin J Ophthalmol, 2016, 52: 663-668)

To compare the corneal biomechanical properties of keratoconic and normal eyes, and to explore the changing characteristics in keratoconic eyes.

Case-control study. Thirty-two keratoconic subjects(41 eyes)and 41 subjects(41 eyes)with normal corneas were enrolled in this study. Scheimpflug noncontact tonometry(Corvis ST)was performed to measure the length of Appl 1(1st A length), velocity of Appl 1(Vin), length of Appl 2(2nd A length), velocity of Appl 2(Vout), deformation amplitude(DA), peak distance, and radius. Comparison of the biomechanical property values between the keratoconic and normal eyes was performed using One-Way ANOVA. Pearson or Spearman correlations were used to evaluate the relationship between corneal biomechanical properties and corneal morphology parameters. The areas under ROC curves of the biomechanical properties of Corvis ST were calculated.

In the keratoconic group, the values of Vin, Vout, and DA were(0.201±0.268),(0.463±0.121), and(1.146±0.113)mm, respectively, which were obviously greater than the normal group[(0.151±0.017),(0.418±0.060), and(1.146 ± 0.113)mm, respectively; F=6.028, 20.724, 10.606, P=0.016, 0.000, 0.001]. The radius in the keratoconic eyes was(5.898 ± 0.976)mm, apparently shorter than the normal eyes[(7.012 ± 0.728)mm; F=5.277, P=0.023]. In the keratoconic eyes, there were significant correlations between the 1st A length, Vout, DA, radius and the thickness of the thinnest cornea(r=0.330,-0.490,-0.482, 0.676, P=0.035, 0.001, 0.001, 0.000). There were significant correlations between the DA, radius and the anterior surface refractive power Km(r=0.751,-0.528, P=0.044, 0.019). The Vin, Vout, DA, and radius had statistically significant correlations with the maximum posterior surface elevation(r=0.475,-0.552,-0.399, 0.273, P=0.021, 0.015, 0.001, 0.000). The areas under ROC curves of the radius, DA, Vout, and Vin were all greater than 0.9.

There were obvious changes of corneal biomechanical properties in keratoconic eyes compared with normal eyes. The radius showed a better sensitivity for the change of corneal biomechanical properties and a major reference value for the diagnosis of keratoconus. (Chin J Ophthalmol, 2016, 52:669-673)

To establish a finite-element biomechanical model of astigmatic keratotomy, and to investigate the impact of surgical parameters on corneal deformation, stress distribution and astigmatism correction.

With Rhinoceros modeling and Abaqus finite element analysis software, a three-dimensional finite-element model of astigmatic cornea was developed, and surgical parameters such as incision optical zone, incision depth and length were varied. Postoperative corneal stress, apical deformation and astigmatism correction were assessed.

A significant increase of stress was noticed near corneal incisions, and maximum corneal stress decreased with the increase of incision depth. Both anterior and posterior corneal surface moved slightly forward postoperatively. Maximum corneal stress was 340 392, 361 022 and 214 187 Pa, and anterior and posterior apical deformation was 49.80, 51.64, 55.53 μm and 54.15, 55.91, 59.67 μm, with 45°, 60° and 90° in arc length of the incision, respectively. The refractive power decreased in steep meridian and increased in flat meridian, resulting in a total decrease of corneal astigmatism. The magnitude of astigmatism correction was 0.85, 1.59, 2.23 and 3.06 D with 30°, 45°, 60° and 90° in arc length of the incision, respectively.

The finite-element biomechanical model of astigmatic keratotomy could be used to predict the optical outcomes after surgery. The magnitude of astigmatism correction is positively correlated with the surgical incision arc length. (Chin J Ophthalmol, 2016, 52: 674-680)

To evaluate and compare the anterior corneal asphericity after small incision lenticule extraction(SMILE)and femtosecond laser in situ keratomileusis(FS-LASIK).

In this case-control study, 45 subjects who underwent SMILE operation comprised the study group, and 33 subjects with FS-LASIK operation comprised the control group. The asphericity coefficient Q-value of the right eyes in both groups was measured at diameters of 6, 7, 8 and 9 mm, respectively, before surgery and at 1 day, 1 week, 1 month and 6 months following surgery. The correlation between the variation of Q-value and the central cutting depth was analyzed.

The Q-value of anterior corneal surface was 0.85 ± 0.31, 0.80±0.28, 0.69±0.25 and 0.51±0.23 after SMILE, and 1.13±0.56, 1.01±0.47, 0.80±0.39 and 0.51±0.31 after FS-LASIK at 1 week. In both groups, the Q-value was significantly different before and after surgery(P< 0.05); there were interaction effects between the operation method and time; the difference between the two groups at 6-mm and 7-mm diameters was statistically significant(P<0.05). The variation of the Q-value before and after operation(ΔQ)showed significant difference(P_6mm=0.004, P_7mm=0.014)between the two groups at 6-mm and 7-mm diameters. The cap diameter of the SMILE group was smaller than that of the FS-LASIK group, but the cutting depth was larger. There was no correlation between ΔQ and the cap/disc diameter. It showed a linear relationship( P<0.05)between ΔQ and the central cutting depth at all examined diameters in the two groups, and the relation degree in the FS-LASIK group was superior to the SMILE group.

Both SMILE and FS-LASIK operations can change the negative Q-value of the anterior corneal surface to the positive. The impact of SMILE on the asphericity is smaller than that of FS-LASIK. (Chin J Ophthalmol, 2016, 52: 681-685)

To evaluate the effect of thiazovivin, a novel ROCK inhibitor, on the morphology and function of human corneal endothelial cells(HCECs).

The primary HCECs were identified by light microscopy and immunofluorescence staining of neuron-specific enolase. To screen the optimal concentration and action time of thiazovivin for maintaining the morphology and function of primary HCECs, Na ⁺/K ⁺-ATPase and N-cadherin were chosen as indicators, and the morphology and function of HCECs in various concentrations(0 μmol/L, 2 μmol/L, 4 μmol/L, and 6 μmol/L)for different durations(24 h and 48 h)were examined by immunofluorescence experiments. The effect of thiazovivin on the expression of ROCK was investigated by immunofluorescence and Western blot.

The primary HCECs cultured were hexagonal, closely packed, homogeneously and obviously stained by neuron-specific enolase. The immunofluorescence staining of Na⁺/K⁺-ATPase showed that when the primary HCECs cultured with various concentrations of thiazovivin(0, 2, 4, 6 μmol/L)for 24 h, the fluorescence were obvious, and the average absorbance values( A)were 1.27±0.08, 3.72±0.17, 21.07±4.67, 3.69±0.34, respectively. And the immunofluorescence staining of N-cadherin revealed that when the primary HCECs treated with 4 μmol/L thiazovivin for 24 h, the cell boundary was clear and the structure of the cells was intact. While the treating time of thiazovivin(4 μmol/L)on HCECs extended to 48 h, the immunofluorescence staining of Na ⁺/K⁺-ATPase and N-cadherin showed that compared to HCECs treated with thiazovivin(4 μmol/L)for 24 h, the fluorescence intensity did not change significantly, but the cells arranged slightly untidy. In addition, the immunofluorescence staining of ROCK was weakened and the expression of ROCK was reduced by thiazovivin. Thiazovivin was effective for protecting the morphology and function of HCECs. An optimal improvement in the morphology, connection and function of HCECs was found when the primary HCECs were cultured with 4 μmol/L thiazovivin for 24 h. Moreover, the expression of ROCK protein could be significantly inhibited by thiazovivin. (Chin J Ophthalmol, 2016, 52: 686-692)

Pterygium is a common and frequently occurring disease in ophthalmology, especially in the Tibet Plateau (above 3 000 m above sea level). The chronic inflammatory reaction of conjunctiva caused by ultraviolet irradiation, wind and sand, dry climate, etc. may damage the limbal epithelial tissue and the incidence is high. Surgery is the main treatment method at present, and the choice of surgical procedure is particularly important, because surgical treatment must achieve three main objectives (1) The pterygium should be safely removed clean. (2) Good optical effect is achieved. (3) Avoid recurrence. There are many traditional methods to treat pterygium, but the recurrence rate is high. Vaniscotte reported in 1986 that the success rate of different surgical methods was 59% with one resection, 82% with bulbar conjunctival transplantation, and 87.5% with autologous conjunctival metastasis^[1]。 The establishment and development of the theory of limbal stem cells in recent years pointed out that the root cause of the occurrence and recurrence of pterygium lies in the dysfunction of limbal stem cells. Conjunctival transplantation with limbal stem cells is an effective method to reconstruct ocular surface function. It can not only effectively provide bulbar conjunctiva, but also provide a healthy epithelial source for the limbus in the diseased area, and restore the function of normal limbus in the diseased area, thus effectively preventing abnormal limbal tissue proliferation, preventing pterygium recurrence, and achieving the purpose of treatment. Since 2011, the Department of Ophthalmology of Lhasa People's Hospital has carried out pterygium resection combined with autologous corneal epithelial tissue transplantation to treat 78 patients (86 eyes) with primary and recurrent pterygium, and achieved ideal results, which are reported below.

Fungal keratitis accounts for 62% of infectious keratitis, ranking first in China. The pathogens are mainly Fusarium and Aspergillus, about 70% of which are Fusarium^[1]。 In the past, due to the lack of high-efficiency commercial antifungal eye drops, the therapeutic effect is poor and the blindness rate is high. Antifungal drugs are classified into polyene antifungal drugs, azole antifungal drugs, echinococcin antifungal drugs, pyrimidines, immunosuppressive antifungal drugs, etc.

Keratoconus is a non-inflammatory corneal disease characterized by corneal dilation. deep anterior lamellar keratoplasty (DALK) has a low incidence of rejection and is currently the first choice for the treatment of completed keratoconus. There are no reports of recurrence after keratoconus surgery in China, but there are few reports after PK and DALK surgery abroad. A case of recurrence of keratoconus after deep lamellar keratoplasty of keratoconus was treated in the Department of Keratology of Hebei Eye Hospital, which is reported as follows.

The patient was a 40-year-old male. Admitted for 4 months due to visual loss in the right eye. The patient experienced visual loss in the right eye without obvious trigger 4 months ago, without other discomfort; One month ago, the visual acuity of my right eye decreased to the point that I could only see the things placed in front of my eye clearly, and at the same time, I obviously felt the linear objects swimming in front of my eye. I went to the ophthalmology clinic of the Fourth Hospital of Xi' an. My intraocular pressure was measured at 56 mmHg (1 mmHg =0.133 kPa), and I was admitted with glaucoma in my right eye. Have a history of close contact with dogs, cats and other animals; The sanitary conditions in mountainous areas are poor, and "dry toilets" are used daily. Past history: 3 years ago, my left eye was injured by a branch, but I was not treated. Now I am blind in my left eye. Ophthalmological examination: visual acuity of right eye 0.6, intraocular pressure 49.8 mmHg, conjunctival hyperemia, corneal edema, about 4 CT in the center of the anterior chamber and 1 CT in the periphery, wide angle, clear iris texture, round pupil, about 5 mm in diameter, slow reflection of light, transparent lens, migrating translucent linear worms can be seen in the upper vitreous cavity, pale papilla color, cup-to-disc ratio 0.9, flat retina, foveal reflection diffuse. There was no light sensing in the left eye, intraocular pressure was 51.6 mmHg, conjunctiva was congested, scleral staphyloma was seen on the nasal side of the sclera, the cornea was porcelain white, and the remaining structure was unclear. Auxiliary examination: Photographic examination of the fundus of the right eye, see the translucent thread-like living worm body in the upper vitreous cavity (Figure 1)； The B-ultrasound examination of the right eye showed vitreous opacity, showing a strip-shaped strong echo (Figure 2)。 Right eye field examination: tubular field, MD-32.58 dB, PSD 4.00 dB; CT and abdominal B-ultrasound of the skull and lungs showed no abnormalities.

The patient was an 89-year-old female. On April 3, 2015, he went to Tianjin Eye Hospital because he found that the tumor on the right eye surface had grown with no vision for more than 20 years. On March 27, 2015, he went to the Department of Ophthalmology, Xiqing Hospital, Tianjin, and underwent a biopsy of right conjunctival mass. The histopathological diagnosis was: squamous epithelial papilloma of right conjunctiva. He had suffered from hypertension for 15 years and coronary heart disease for 10 years, and no obvious abnormalities were found in the systemic physical examination. Eye examination: binocular vision examination cannot cooperate; There is no congestion in the conjunctiva of the right eye, and papillary neoplasms can be seen on the surface of the cornea and bulbar conjunctiva. The medial edge originates from the medial canthus, with a volume of about 20 mm ×8 mm ×3 mm, pink color, smooth surface, and a large number of tortuous blood vessels can be seen, which are soft in texture, with poor borders and cannot be pushed (Quintessence Picture 1)； Other structures in the eye cannot be peeped into. CT examination of both eyes in transverse axis: bilateral eyelids were thickened, and circular soft tissue density shadow was visible in front of the cornea of the right eye, with poor border and homogeneity, and the CT value was about 44 HU. Clinical diagnosis: squamous epithelial papilloma of the conjunctiva of the right eye.

The usual method of checking blepharitis patients for Demodex infection is to remove eyelashes, observe them under a light microscope and count them (Quintessence Picture 1)。 The invasiveness of this method, the pain caused by sampling, and the inability to take out all Demodex mites at the sampling site often limit the doctor's grasp of the overall situation of infection. Laser confocal microscopy can directly observe the infection of Demodex mite at the site of Demodex mite infection and the meibomian gland, and clearly show the number and morphology of Demodex mite (Quintessence Picture 2), which makes up for the lack of traditional examination methods, and has the characteristics of non-invasive, convenient and comprehensive.

The cylinder cells at the bottom of corneal epithelial cells are basal cells. Their cytoplasm contains keratin intermediate filament which is important in secretion of basement membrane. Corneal epithelial dysfunction due to diabetes or ocular surgery is intimately related with basal cell abnormality. Corneal epithelial basement membrane is a highly specific extracellular matrix which is made up of lamina lucida and lamina densa. It plays an extremely important role in renewal and restoration. Many ocular abnormalities and diseases have been described to relate to the corneal epithelial basement membrane, such as traumatic recurrent corneal erosion, corneal dystrophy and keratoconus. (Chin J Ophthalmol, 2016, 52: 703-707)

Stevens-Johnson syndrome(SJS)and toxic epidermal necrolysis(TEN)are life-threatening cutaneous adverse drug reactions that induce widespread epidermal necrosis. Ocular and cutaneous diseases are common chronic sequelae of SJS and TEN. Several concepts have been proposed to explain the pathogenesis of severe cutaneous adverse drug reactions. Recent advances in genetic, pharmacogenomics and immunologic studies have provided evidences of genetic predispositions, drug metabolism and cytokines related to SJS and TEN. With regard to keratinocyte death, several cell death mediators, such as Fas/FasL, granulysin and TNF, have been proposed to play an important role in the pathogeneses of SJS and TEN. A subset of T lymphocytes, including regulatory T cells, may also play a role. This review summarizes the pathogeneses of SJS and TEN mainly from the aspects of genetic susceptibilities, drug metabolism, and immune cells and cytokines. (Chin J Ophthalmol, 2016, 52: 708-713)

The retinal ganglion cell, due to peculiar structural and energetic constraints, appears acutely susceptible to mitochondrial dysfunction. Emerging evidence suggests that changes in the mitochondrial DNA(mtDNA)and in nuclear DNA genes that encode mitochondrial proteins may influence mitochondrial structure and function and, therefore, contribute to the pathogenesis of primary open angle glaucoma. As the main glaucoma risk factors are elevated intraocular pressure and older age, we discuss their relationship with mitochondrial dysfunction. If the contribution of mitochondrial dysfunction to glaucoma pathogenesis is further established, emerging therapies aiming to optimize mitochondrial function represent potential clinical treatments. (Chin J Ophthalmol, 2016, 52: 714-717)

The 17th National Conference on Cataract and Intraocular Lens of Chinese Medical Association, sponsored by the Ophthalmology Branch of Chinese Medical Association and the Cataract and Intraocular Lens Group of the Ophthalmology Branch of Chinese Medical Association, and jointly organized by Shaanxi Medical Association and the Ophthalmology Center of the Second Affiliated Hospital of Zhejiang University School of Medicine, was held in Xi' an from May 26 to 28, 2016. This session was attended by dozens of ophthalmologists, more than 1,800 registered representatives and more than 500 manufacturer representatives from home and abroad.