Volume 58 · Issue 02 · 2022

This issue focuses on the research progress in the diagnosis and treatment of ocular surface diseases. The responsible editorial board member in charge of the planning, composition and review of this issue is Professor Xu Jianjiang, who published an expert review "Focusing on the Differential Diagnosis of Superficial Punctate Keratopathy" in this issue. Superficial punctate keratopathy is a common abnormality of corneal epithelium and superficial stromal layer in clinic. There are many primary diseases that cause superficial punctate keratopathy in clinic and their pathogenic mechanisms are different, resulting in very different treatment options. Therefore, this article points out that the differential diagnosis of primary diseases is particularly important, which is the key link in the diagnosis and treatment of superficial punctate keratopathy. However, the symptoms and signs of superficial punctate keratopathy lack specificity, so it is necessary to raise awareness, adopt correct diagnostic ideas, inquire about medical history and conduct various related examinations, comprehensive analysis, strip the cocoon, see the essence through the phenomenon, trace the root source, and find out the primary disease, so as to give targeted treatment, promote the repair of corneal epithelium as soon as possible and improve the prognosis.

Superficial punctate keratopathy is a common ocular abnormality with the corneal epithelium and superficial corneal stroma involved. Various primary diseases can lead to superficial punctate keratopathy. Therefore, the differential diagnosis of the etiologies of superficial punctate keratopathy is crucial. Due to the absence of specific symptoms and signs, it is important to have an overall recognition of the disease and adopt necessary examinations for differential diagnosis. Acquisition of a detailed medical history, slit-lamp examination, in vivo laser scanning confocal microscopy, and other diagnostic tools should be combined to make an accurate diagnosis of the primary disease of superficial punctate keratopathy and provide objective evidences for the determination of treatment regimen.

Dry eye is a common ocular surface disease worldwide that affects the patients′ visual quality and life quality. Correctly distinguishing its etiology, severity and subtypes is the basis for precise diagnosis and effective treatment. This article summarizes the challenges and bottlenecks in the development of dry eye precise diagnosis, and discusses the current situation and development trend of dry eye diagnosis from traditional evaluation methods to novel diagnostic techniques, aiming to provide reference and guidance for promotion of clinical precise diagnosis of dry eye.

Immune-related keratopathy is a type of corneal disease caused by systemic or ocular immune disorders, with abnormal immune response to normal or degenerated corneal tissue, leading to the damage to ocular structure and function and the visual impairment. It mainly includes Mooren′s ulcer, blepharokeratoconjunctivitis, and peripheral corneal ulcer associated with rheumatoid arthritis or other systemic immune diseases. Due to the diverse clinical manifestations, repeated and prolonged disease course, and high misdiagnosis and missed diagnosis rates, immune-related peripheral keratopathy often has a poor prognosis. The Cornea Group of Ophthalmology Branch of Chinese Medical Association has convened experts to discuss and reach the current consensus, focusing on the principle of diagnosis, differential diagnosis, and treatment of immune-related peripheral keratopathy, which would play an important clinical guiding role in the early detection, timely intervention, and proper treatment of the disease.

Myopia is a focal issue affecting the eye health of children and adolescents in China. Hyperopia reserve is the refractive state before the occurrence of myopia. As the result of dynamic matching between the axial length, cornea and lens, it is of great significance to the prevention and control of myopia. There has been a lack of the reference basis for children′s eyeball development parameters and the influence of genetic factors, especially the changing law of the above-mentioned parameters in the process of children′s "emmetropization". To promote the prevention and control of myopia in children and adolescents and to standardize population screening and clinical treatment, based on the survey data of refractive errors in children and adolescents from different regions, a consensus has been reached on the reference interval of hyperopia reserve, axial length and corneal curvature and related genetic factors of emmetropia at different ages among school-age children by the Public Health Ophthalmology Branch of the Chinese Preventive Medicine Association.

To identify and analyze imaging features of posterior polymorphous corneal dystrophy (PPCD) by in vivo confocal microscopy (IVCM).

This retrospective case series enrolled 27 eyes of 18 patients (including 10 males and 8 females) who were diagnosed with PPCD at the Department of Ophthalmology in Peking University Third Hospital between January 2013 and December 2019. The mean age was (23.61±14.81) years. There were 9 monocular and 9 binocular cases. All patients were examined by slit-lamp biomicroscopy and IVCM. The visual acuity, the mean endothelial cell density, and the images of IVCM were analyzed in all cases.

The mean best-corrected visual acuity was 0.76±0.33, and the mean endothelial cell density was (1 723.6±698.3) cells/mm². The IVCM images of type 1 PPCD (vesicular lesions) showed hyperreflective, placoid or homocentric lesions at the level of the Descemet′s membrane, hyporeflective, oval or round lesions at the level of the Descemet′s membrane, and hyporeflective, crater-like lesions at the level of the endothelial cell layer. The IVCM images of type 2 PPCD (band lesions) displayed hyperreflective, band lesions and a fibrous strand structure at the level of the Descemet′s membrane, hyporeflective, vesicular lesions at the level of the Descemet′s membrane, and hyporeflective, trough-and ridge-like lesions at the level of the endothelial cell layer. The IVCM images of type 3 PPCD (geographic placoid opacities) showed loss of the hexagonal features of endothelial cells and epithelial-like cell transformation.

PPCD primarily affects the endothelium and Descemet′s membrane. IVCM could highlight the special characteristics of PPCD including hyperreflective lesions at the level of the Descemet′s membrane, hyporeflective lesions at the level of the endothelial cell layer, and epithelial-like cell transformation of endothelial cells. IVCM is an invaluable tool for clinical diagnosis and dynamic monitoring of PPCD.

To investigate the early histological changes by confocal microscopy of patients with advanced keratoconus receiving collagen cross-linking therapy.

In this prospective case series study, confocal microscopy was used to observe 23 patients (32 eyes) who were diagnosed with advanced keratoconus and treated with collagen cross-linking at the Department of Ophthalmology, Chinese PLA General Hospital from September 2017 to March 2019, aged (26±10) year. All patients were examined before and at 1 week, 1 month and 3 months after the therapy. The tissue structure changes, the density of nerve fibers, stromal cells and endothelial cells, and the depth of the corneal stroma were recorded and compared. The overall differences at different times were compared by repeated measurement analysis of variance or Friedman test, and the pairwise comparison was corrected by LSD-t test or Bonferroni test.

One week after collagen cross-linking, the epithelial cells were in the repair stage, showing an increased nucleolar size and an enhanced reflection, and the activated cells could be detected under the epithelium. The superficial corneal stroma was swollen and spongiform, while the deep corneal stroma was patchy or cord-like, scattered and with a strong reflection. One month after the therapy, epithelial cells recovered, subepithelial nerves began to grow, the superficial corneal stroma still showed a spongy structure, and the reflection was further enhanced. The activation of the deep corneal stroma exhibited as thicker plaques or cord-like structure. Three months after the therapy, the continuous elongation of single nerve fibers could be detected occasionally. There was statistically significant difference in the density of nerve fibers before and early after the therapy (F=233.30, P<0.001). Compared with the preoperative value [(14.60±2.57) mm/mm²], the density of subepithelial nerve fibers decreased significantly in the early postoperative period, which was (0.51±0.31), (3.65±2.21) and (8.50± 4.02) mm/mm², respectively, at 1 week, 1 month and 3 months, and there were significant differences between different time points (all P<0.05). There was also statistically significant differences in the density of anterior stromal cells before and early after the therapy (χ²=92.48, P<0.001). Compared with the preoperative value [347.00(345.00,395.75) cells/mm²] the density of anterior stromal cells decreased significantly in the early postoperative period, which was 2.00(1.00,5.75), 2.50(1.00,5.75) and 79.00(64.25,94.00) cells/mm², respectively, at 1 week, 1 month and 3 months, and there were significant differences between different time points (all P<0.05). Within 3 months after the therapy, the depth of the corneal stroma observed by confocal microscopy ranged from 245 to 536 μm, with an average of (400.56±86.12) μm. Histologically, the depth of the corneal stroma ranged from 245 to 536 μm [average, (402.13±89.20) μm], from 251 to 527 μm [average, (399.88±85.92) μm] and from 259 to 530 μm [average, (399.69±85.94) μm] at 1 week, 1 month and 3 months, respectively, with no significant difference (F=0.797, P=0.455). There was no significant difference in the density of posterior stromal cells [(260.6±33.2) cells/mm² preoperatively, (264.4±44.5) cells/mm² at 1 week, (263.9±37.6) cells/mm² at 1 month and (266.3±40.2) cells/mm² at 3 months] and endothelial cells [(2 707±152.6) cells/mm² preoperatively, (2 704±148.5) cells/mm² at 1 week, (2 705±152.6) cells/mm² at 1 month and (2 704±150.1) cells/mm² at 3 months] between different time points (F=1.380, 1.011; P=0.259, 0.351).

Confocal microscopy is able to clearly document the early morphological characteristics after collagen cross-linking in the treatment of keratoconus, including the epithelial and subepithelial nerve injury repair, the spongiform superficial corneal stroma, the patchy or cord-like deep corneal stroma, and the relatively stable stromal depth change.

To establish a method to record the spontaneous blink pattern with a machine learning model, and to clarify the spontaneous blink pattern in patients with dry eye.

It was a cross-setional study.We selected 357 dry eye patients (102 males and 255 females), aged (46.2±13.3) years, who visited corneal specialist clinics of Beijing Tongren Eye Center in 2019, as the dry eye group. The control group enrolled 152 normal controls, including 32 males and 120 females, aged (48.1±13.9) years. All participants completed the Ocular Surface Disease Index questionnaire, blink video capture, lipid layer thickness measurement, tear break-up time measurement, corneal fluorescein staining, and Schirmer Ⅱ test. Based on the assembled model built using UNet image segmentation algorithm and ResNet image classification algorithm, single frames of the blink video were analyzed, and then the palpebral opening height of each frame was obtained in order to establish a spontaneous blink wave. Finally, the characteristics of spontaneous blinks in dry eye patients were analyzed based on different types of complete blinks (types A, B and C) and partial blinks (types Ⅰ, Ⅱ and Ⅲ). Independent sample t test and Wilcoxon rank-sum test were used to judge if there was significant difference between the dry eye group and the normal group.

The accuracy of the segmentation model and the classification model was 96.3% and 96.0%, respectively, and the consistency with the manual analysis was 97.9%. In dry eye patients, the number of blinks was 30 (18, 42)/min, which was higher than that in normal controls [20 (9, 46)/min] (U=18 132.50, P=0.002). The number of complete blinks in dry eye cases was significantly lower than that in normal controls [6 (3, 24)/min vs. 12 (3,33)/min; U=12 361.00, P=0.016], and the number of partial blinks was significantly higher than that in normal controls [15 (6, 27)/min vs. 3 (0, 10)/min; U=22 839.00, P<0.001]. In complete blinks, the proportion of type A blinks in dry eye patients was significantly higher than that in normal controls [53.7% (2 796/5 177) vs. 39.3% (633/1 698); χ²=101.83, P<0.001]; in partial blinks, the proportion of type Ⅱ blinks in dry eye patients was significantly higher than that in normal controls [36.0%(2 334/6 477) vs. 29.6%(126/426); χ²=6.99, P=0.007]. The average interblink interval of dry eye patients was 1.2 s, which was not significantly different from that of normal controls (1.1 s; U=15 230.00, P=0.093). The eyelid closed phase of dry eye patients was 0.8 s, which was significantly shorter than that of normal controls (1.3 s; U=16 291.50, P=0.006). There were no significant differences in eyelid closing phase, early opening phase and late opening phase between the two groups (all P>0.05).

In dry eye patients, the number of partial blinks increased, the number of complete blinks decreased, and the duration of eyelid closed phase shortened significantly. The main blink patterns of dry eye patients included type Ⅱ partial blinks with a reduced closure amplitude and type A complete blinks with a shortened closure time.

To investigate the efficacy of mitomycin C (MMC) 0.02% for prevention of haze after transepithelial photorefractive keratectomy (Trans-PRK) for mild and moderate myopia.

Retrospective cohort study. We reviewed medical records of 295 patients (588 eyes) who underwent Trans-PRK with or without use of MMC. There were 45 patients (90 eyes) in the mild myopia group (aged between 18 and 41 years; 37 males and 8 females; myopia diopter <3.00 D) and 250 patients (498 eyes) in the moderate myopia group (aged between 18 and 46 years; 168 males and 82 females; myopia diopter: 3.00 to 6.00 D). The two groups were divided into subgroups with MMC 0.02% and without MMC, respectively. The time of intraoperative application of MMC, if there was, was 15 s and 30 s in the mild myopia group and the moderate myopia group, respectively. The mean follow-up time was 6 months. Postoperative best corrected visual acuity (BCVA), spherical equivalent (SE) and haze were analyzed and compared using an independent Student t-test or Mann-Whitney U test between subgroups. Haze variables were compared using chi-square statistics.

Haze was quantified with Fantes from grade 0.5 to 4. In the mild myopia group, all haze grades were 0.5 within 3 months. The incidence of haze was 6.25% (2/32) in eyes treated with MMC and 8.62% (5/58) in eyes treated without MMC; there was no statistical significance (χ²=0.00, P>0.999). In the moderate myopia group, the incidence of haze was 9.19% (24/261) in eyes treated with MMC within 3 months; the grade was 0.5 in 91.67% (22/24) of eyes with haze and 1 in 8.33% (2/24). The incidence of haze was 29.53% (70/237) in eyes treated without MMC; the grade was 0.5 in 60.00% (42/70) of eyes with haze, 1 in 18.57% (13/70), and 2 in 5.71% (4/70) within 3 months, and 0.5 in 15.71% (11/70) after 3 months (χ²=12.36, P=0.002). In the mild myopia group, BCVA was 5.0(5.0, 5.1) versus 5.0(5.0, 5.1) in the subgroups with MMC and without MMC (Z=-0.34, P=0.733). In the moderate myopia group, BCVA was 5.0(5.0, 5.1) versus 5.0(5.0, 5.1) in the subgroups with and without MMC (Z=-2.05, P=0.040). In the mild myopia group, SE was (0.33±1.07) D versus (0.32±0.57) D in the subgroups with and without MMC (t=0.25, P=0.805). In the moderate myopia group, SE was (0.66±0.85) D versus (0.53±0.67) D in the subgroups with and without MMC (t=2.97, P=0.003).

MMC 0.02% was effective in preventing haze after Trans-PRK in the treatment of moderate myopia. However, it was not effective in mild myopia.

To evaluate the effect of femtosecond laser-assisted corneoscleral lamellar keratoplasty (FL-CSLK) on peripheral corneal disease (PCD).

Retrospective cohort study. Six patients (6 eyes) with PCD who underwent FL-CSLK in Qingdao Eye Hospital from March 2014 to March 2017 were grouped as the FL-CSLK group, including 4 males and 2 females, aged (46.7±17.9) years. In addition, 8 patients (8 eyes) with PCD who underwent traditional corneoscleral lamellar keratoplasty in the same period were included in the control group. The items for analyses were as follows: visual function recovery, including visual acuity, equivalent spherical power, and astigmatism; the state of the cornea, including the healing time of the corneal epithelium, the transparency of the graft, the thickness of the corneal graft and implant bed, and the loss rate of corneal endothelial cells; intraoperative and postoperative complications, including high intraocular pressure, interlayer effusion, delayed corneal epithelial healing, immune rejection, and primary recurrence. Paired t-test was used to compare the best corrected visual acuity (BCVA), equivalent spherical power, and astigmatism before and after operation. The BCVA and corneal graft epithelial healing time between the two groups were compared by independent sample t-test.

The 6 patients in the FL-CSLK group included 2 cases of Mooren ulcer, 3 cases of Terrien marginal degeneration, and 1 case of pellucid marginal degeneration. The control group consisted of 4 eyes with Mooren ulcer and 4 eyes with Terrien marginal degeneration. The BCVA (logarithm of the minimum angle of resolution) in the FL-CSLK group was 0.35±0.09 at 6 months after operation, which was significantly higher than that before operation (1.17±0.15; t=9.01, P<0.001) and at 6 months after operation in the control group (0.78±0.29; t=-3.96, P=0.003). The equivalent spherical power was (4.8±2.7) D, lower than that before operation (t=-3.71, P=0.014), and the astigmatism power was (10.1±4.1) D, lower than that before operation (t=6.04, P=0.002) in the FL-CSLK group. The healing time of the graft epithelium in the FL-CSLK group and control group was (8.5±3.3) days and (12.8±6.1) days, respectively, with no significant difference (t=-1.54, P=0.149). The central thickness of the graft in the FL-CSLK group was (525±47) μm at 6 months after operation, the central thickness of the implant bed was (189±119) μm, and the loss rate of the corneal endothelium was 7.5%±2.1%. In the control group, 1 case had intraoperative perforation, 2 cases had intracorneal hemorrhage, and 1 case had intracorneal epithelial implantation cysts and graft ulcer. There were no intraoperative and postoperative complications in the FL-CSLK group.

FL-CSLK can yield good clinical results in the treatment of PCD. The smooth optical interface made by femtosecond lasers can help the patient achieve a good visual prognosis. The procedure reduces the risk of corneal perforation and thus improves the surgery safety.

Iridocorneal endothelial syndrome is a rare ophthalmic disease, most of which are unilateral and common in women. The rate of misdiagnosis and missed diagnosis is relatively high due to its various clinical manifestations. In this case, the patient presented uncontrollable high intraocular pressure, corneal edema leading to difficult observation of corneal endothelium morphology, and accompanied by a small amount of iris neovascularization. No clearly diagnosis was made before glaucoma surgery. Further examination was performed after corneal clearance, and the final diagnosis was iris corneal endothelial syndrome (Chandler syndrome).

Dry eye is the most common disease in ophthalmic clinics besides refractive error, which seriously affects the life quality of patients and has become an important public health problem in China. Dry eye as a kind of multifactorial disease can be induced or accelerated by contact lens wear, which is considered as one of the risk factors of dry eye. Studies have shown that the incidence of dry eye is higher in contact lens wearers than in normal people. In 2017, the Tear Film and Ocular Surface Society included contact lens-associated dry eye (CLADE) in the iatrogenic dry eye for the first time, and its importance is evident. However, ophthalmologists mostly used to focus on serious complications such as keratitis caused by contact lens wear, and CLADE has not been well valued and understood. This article reviews the latest studies on the epidemiology, pathogenesis, diagnosis, prevention, and treatment of CLADE.

The complex components of ocular surface tissue, its cells, extracellular matrix and other layers are fused into a whole, collectively referred to as ocular surface microenvironment, and its homeostasis plays a key role in maintaining ocular surface health. The occurrence of dry eye often starts with changes in the microenvironmental components of the ocular surface, resulting in imbalance of ocular surface homeostasis. In this paper, the pathophysiological process of dry eye is analyzed based on the ocular surface microenvironment, so as to help the correct clinical diagnosis and accurate treatment of dry eye.