Volume 58 · Issue 08 · 2022

This issue focuses on the research progress in the diagnosis and treatment of ocular surface diseases. The responsible editorial committee responsible for the planning, composition and review of this issue is Professor Jieying.

Blepharokeratoconjunctivitis, (BKC) is a common ocular surface chronic inflammatory disease in children. It can cause eye irritation or even visual impairment. At present, the etiology of BKC in children is not clear and relevant studies are in the initial stage, consequently, there has not been an authoritative applicable expert consensus in China. Compared with adults, the clinical manifestations of pediatric patients are often atypical, coupled with the lack of understanding, so inadequate diagnosis and treatment are still exist in pediatric BKC. This article reviews the etiology, diagnosis and treatment status, clinical characteristics, standardized diagnosis and treatment of pediatric BKC, in order to arouse the attention of ophthalmologists.

Pediatric keratoplasty is a highly challenging and demanding procedure in children because of various intraoperative morphologic and functional factors and postoperative complications. However, it remains the only way to promote visual development and to avoid corneal blindness in infants and children with corneal opacities. Corneal transplantation in children is different from that in adults in many aspects, such as surgical techniques and clinical evaluation. Besides, it poses more emphases on the perioperative management and the long-term follow-up, because children are less cooperative when examined and are not readily complaining about symptoms. This article is aimed to provide a consensus concerning the indications, preoperative evaluation, surgical procedures and postoperative management regarding pediatric keratoplasty. The consensus, which is based on the results from discussions and consultations among domestic leading researchers and experts with extensive experiences in the related areas, targets to standardize the procedure of pediatric keratoplasty in clinical practice, to minimize the risk of graft failure and to achieve promising outcomes.

Epidemiological studies have confirmed that the incidence of dry eye is closely related to lifestyles. The Expert Consensus on Dry Eye in China: Definition and Classification (2020) incorporated lifestyle-related factors into the classification of causes and risk factors for dry eye. In order to improve the diagnosis, treatment and prevention of this type of dry eye, the experts from the Chinese Branch of the Asian Dry eye Society and other scientific organizations have formed a consensus on the definition, classification, incidence, epidemiology, pathological mechanism, clinical characteristics, diagnosis, treatment and prevention of lifestyle-related dry eye. This consensus can be used as a reference for clinical work.

To evaluate the diagnostic efficacy of stress-strain index (SSI) for different stages or degrees of keratoconus and changes of SSI and stiffness parameter A1 (SPA1) after corneal collagen cross-linking (CXL) surgery.

Cross-sectional study and retrospective case series study. Ninety-four patients (113 eyes) diagnosed as clinical keratoconus (CKC) in Qingdao Eye Hospital from July 2019 to August 2021 were enrolled in the CKC group, including 69 males and 25 females, aged (20.82±4.53) years, and further divided into subgroups of mild (35 patients, 36 eyes), moderate (36 patients, 40 eyes) and severe (33 patients, 37 eyes) CKC. Fifty-six unaffected eyes of monocular keratoconus patients were enrolled in the subclinical keratoconus (SKC) group. Ninety-one healthy subjects (91 eyes) were recruited as the control group. All subjects were examined by Pentacam topography and Corvis ST measurements to obtain mean keratometry, maximal keratometry, deformation amplitude (DA) ratio at 2 mm, integrated radius (IR), Ambrósio′s relational thickness to the horizontal profile, corneal central thickness, SPA1 and SSI for comparison. Forty-eight CKC patients (65 eyes) underwent CXL surgery, and the above parameters were recorded before and 3, 6 and 12 months after operation. Data were analyzed by the ANOVA test, Kruskal-Wallis H test, paired sample test, receiver operating characteristic curves and Pearson correlation.

The value of SPA1 in the SKC group accounted for 85.53% (87.92±12.38 vs. 102.79±11.74; t=-6.614, P<0.001) compared with the control group, but the value of SSI had no difference in the two groups (t=0.105, P=0.916). The value of SPA1 in the CKC group accounted for 52.87% (54.35±14.70 vs. 102.79±11.74; t=25.985, P<0.001) compared with the control group. The value of SSI in the CKC group accounted for 67.96% (0.70±0.14 vs. 1.03±0.14; t=-15.305, P<0.001) compared with the control group. The more severe the disease was, the smaller the SPA1 and SSI values were 64.27±12.12, 55.22±12.23, 43.75±12.33; 0.78±0.14, 0.71±0.11, 0.61±0.09, and there were significant statistical differences among groups (mild vs. moderate, mild vs. severe, moderate vs. severe; SPA1: t=3.257, -7.249, -4.159; all P<0.001. SSI: t=2.383, 5.065, 2.798; P=0.018,<0.001,=0.006). Receiver operating characteristic analysis showed that SPA1 had good diagnostic efficiency for subclinical patients [area under curve (AUC)=0.802], while the SSI had no diagnostic value (P=0.802). SPA1 had better diagnostic efficiency than the SSI for keratoconus in different stages, especially in the mild CKC and SKC groups (AUC: 0.914 vs. 0.847). The SSI had a significant positive correlation with SPA1 and a significant negative correlation with DA ratio and IR in the control, SKC and CKC groups (r=0.278, 0.368, 0.550; r=-0.346, -0.462, -0.547; r=-0.612, -0.591, -0.718; P<0.01). For patients who received CXL, maximal keratometry decreased significantly at 6 and 12 months postoperatively (t=4.029, 3.633; all P<0.001), whereas SPA1 increased significantly (t=-3.960, -4.500; all P<0.001). However, the SSI only increased significantly at 3 months (t=-2.577, P=0.012) and returned to the preoperative level at 6 and 12 months postoperatively, with no statistical difference compared with the preoperative level (t=-0.544, -0.257; P=0.589, 0.798).

While there was no significant change in the SSI of SKC, the SSI of CKC decreased, and the more severe the disease was, the smaller the value was. The SSI was significantly and consistently correlated with DA ratio, IR and SPA1. The SSI compared with SPA1 had a lower degree of identification in different stages and degrees of keratoconus. The consistency of SPA1 with clinical effects after CXL surgery was higher than that of the SSI parameter.

To evaluate the characteristics of ocular injury in patients with severe extensive thermal burns, and to explore the effective methods to prevent and treat corneal ulcers related to severe burns.

A retrospective case series study. Between 2010 and 2019, Sixteen severe thermal burn patients with burn sizes>70% of the total body surface area involving the ocular region were admitted to the Burns and Plastic Surgery Division of Chinese PLA General Hospital, and consult with Ophthalmology Division. There were deep second-degree to fourth-degree burns in the eyelids. In the eleven surviving patients, 22 eyes presented ectropion. Eyelid full-thickness skin grafting (EFTSG) combined with or without tarsorrhaphy was performed in 20 eyes due to severe corneal exposure. Two eyes received partial blepharorrhaphy because of mild ectropion. The ocular manifestations and treatment outcomes were reviewed and assessed.

The majority of the patients were youth, and the average age was (36.8±10.4) years. The burn area was 84.0%±9.1% of the body surface area. Corneal ulcers secondary to lagophthalmos occurred at (35.1±15.6) days after burning in 75% (24/32) of eyes. Perforation was found in 18.8% (6/32) of eyes. Among the 22 operated eyes, the corneal ulcer was repaired in all 9 eyes receiving EFTSG with tarsorrhaphy, whereas ectropion recurred in 8 of 11 eyes only receiving EFTSG, and 4 eyes underwent further surgery due to corneal epithelial defects.

In patients with severe large-area thermal burns, corneal ulcers are common complications. Prevention of corneal exposure is vital because the treatment of corneal ulceration is difficult due to eyelid deformity, inflammation and the absence of donor skin. Timely full-thickness skin grafting and blepharorrhaphy are effective approaches to preventing exposure keratopathy. To severe ulcers occur, conjunctival flap or Tenon′s capsule covering combined with eyelid EFTSG and tarsorrhaphy is useful to rescue visual function.

Objectie To investigate the susceptibility of drug-resistant staphylococci isolated from different parts of the anterior segment to levofloxacin, tobramycin, cefazolin sodium, fusidic acid and clindamycin.

Experimental Study. A total of 67 patients with anterior segment infection (33 cases of conjunctivitis, 6 cases of bacterial keratitis, 7 cases of blepharitis, 9 cases of neonatal dacryocystitis, 9 cases of neonatal dacryocystitis, 1 case of adult dacryocystitis and 11 cases of other infectious eye diseases) were collected from the conjunctival sac, cornea, eyelid margin and lacrimal sac. Minimum inhibitory concentration (MIC) determination of methicillin-resistant Staphylococcus (MRS) strains and β-lactamase-producing (β-Lac) strains by a micro-liquid-based method, according to the M100 standard of the American Institute for Clinical and Laboratory Standardization Susceptibility and resistance determinations were made. Data were statistically analyzed using Chi-square or Fisher′s exact test.

Thirty-five MRS, 30 β-Lac and 2 β-Lac MRS isolates were identified from 67 multidrug-resistant Staphylococcus . There were 3, 9, 4, and 19 MRS isolates isolated from the lacrimal sac, cornea, eyelid margin and conjunctival sac, accounting for 3/4, 9/12, 4/8, 19/43 (44.2%) of the isolated sites respectively. There were 1, 3, 3, and 23 β-Lac isolates, accounting for 1/4, 3/12, 3/8 and 23/43 (53.5%) of the isolated sites, respectively. The highest proportion of β-Lac isolates isolated from patients with a diagnosis of conjunctivitis was 17 (25.3%) from the conjunctival sac. Among the MRS strains isolated from the cornea and lacrimal sac, 5 (7.5%) and 3 (4.5%) were from patients diagnosed with bacterial keratitis and neonatal tear, respectively. The number of MRS strains and β-Lac isolates isolated from patients with a diagnosis of blepharitis were both 3 (4.5%) from the lid margin.Among the strains isolated from the eyelid margin and the conjunctival sac, drug-resistant Staphylococcus epidermidis was the main strain, the drug-resistant Staphylococcus aureus was the major isolates in lacrimal sac and cornea. Among the 35 MRS isoaltes, 25, 24, 12, 12, and 11 were sensitive to cefazolin sodium, fusidic acid, levofloxacin, clindamycin and tobramycin, and the sensitivity rates were 71.4%, 68.6%, 34.3%, 34.3% and 31.4%, the difference was statistically significant (χ²=22.756, P<0.001), The sensitivity rates of levofloxacin, tobramycin, cefazolin sodium, fusidic acid and clindamycin against MRS isolates from the anterior segment were both statistically significant differences (χ²=18.493, 11.594, 8.906, 9.841, 16.059; all P<0.05). The susceptibility rates of MRS isolates against five antibiotics was statistically significant differences (χ²=33.080, P<0.001). Among the 30 β-Lac isolates, 27, 22, 19, 16, and 8 were sensitive to cefazolin sodium, fusidic acid, levofloxacin, tobramycin and clindamycin, and the sensitivity rates were 90.0 % , 73.3%, 63.3%, 53.3% and 26.7%, the difference was statistically significant (χ²=28.280, P<0.001). The sensitivity rates of five antibiotics against β-Lac isolates from the anterior segment were both statistically significant differences (χ²=50.971, 24.543, 48.147, 44.899, 18.676; all P<0.001). The susceptibility rates of β-Lac isolates against five antibiotics was statistically significant differences (χ²=23.383, P<0.001). The sensitivity of cefazolin sodium and fusidic acid against β-Lac isolates were higher than MRS isolates.

Cefazolin sodium and fusidic acid may be the best choice for the treatment of drug-resistant Staphylococcus isolated from anterior conjunctival sac, cornea, eyelid margin and lacrimal sac, especially for β-Lac-producing drug-resistant Staphylococcus infection.

Objective To prepare a biologically active amniotic membrane powder and explore its preservation conditions, and to evaluate the efficacy of the amniotic membrane (AM)-fibrin sealant (FS) cement made from the amniotic powder on the rabbit severe ocular surface alkali burn model. Methods Experimental research. Fresh AM was air-dried, cooled with liquid nitrogen, ground into amniotic powder and sterilized by radiation. The expression of transformed growth factor, nerve growth factor receptor (NGFR), hepatocyte growth factor (HGF), epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) after preparation and 10, 20 and 30 days after storage at room temperature, 4 ℃ and -20 ℃ was tested and compared with that in the fresh AM. The AM-FS cement containing different concentrations of amniotic powder and no amniotic powder was diluted. Rabbit corneal epithelial cells were cultured for 72 hours. The effects of different concentrations of amniotic powder on epithelial cell growth were observed by light microscopy, and the amniotic powder concentration with the largest absorbance value at 450 nm was selected for subsequent animal experiments. Thirty-two right eyes of 32 rabbits as the severe ocular surface alkali burn model were divided using the random counting method into the AM-FS cement group, fresh AM transplantation group, FS group and antibiotic control group (8 rabbits each group) and given different interventions. After weekly observation of corneal repair, hematoxylin and eosin staining, immunohistochemical staining of monocyte chemotaxis protein 1 (MCP-1)and vascular endothelial growth factor (VEGF) were performed and detected by light microscopy at 28 days. The logFC values of the growth factor or receptor expression difference ratio were corrected by BH; the data were analyzed by t-test and analysis of variance.

The expression of TGF in the amniotic membrane powder compared with the fresh amniotic membrane group (logFC=-0.11), and the expression of NGFR (HGF, EGF, bFGF) was higher than that of the fresh amniotic membrane group (logFC=-2.07, 0.72, 0.46, 2.62; P<0.05); the expression of HGF, bFGF and EGF in amniotic membrane powder stored for 10 days and 20 days were no lower than fresh amniotic membrane; at 30 days, the expression of growth factors or receptors except HGF and bFGF were decreased, and HGF, bFGF and EGF were no less than 4 ℃ and -20 ℃.The maximum A value was obtained for 0.25 mg/ml of the amniotic membrane powder after 72 hours of the CEC culture 0.98±0.05. The corneal recovery was better in the AM-FS and fresh amniotic membrane transplant groups, with corneal turbidity scores of 3.75±0.46 and 3.50±0.46, respectively, on 28 days, lower than antibiotics (4.29±0.45) (t=2.480, 3.629; P=0.019, 0.001). The corneal neovascular area in the antibiotic control group was compared with the other three groups (t=4.040, 4.339, 2.820; all P<0.001); the corneal neovascular area in the AM-FS group was (9.88±0.20) and (18.96±0.18) mm² at 7 and 28 days. The corneal neovascularization area at 7 and 28 days in the fresh AM group [(9.54±0.22) and (18.08±0.96) mm²] was smaller than the AM-FS group (t=3.085, 3.017, P=0.005, 0.005). Despite the tiny statistical difference (0.34, 0.88), there was no clinical difference. Hematoxylin and eosin staining showed corneal structures were intact in the AM-FS and fresh AM groups, the epithelial arrangement became normal, and the corneal healing was superior to the FS and antibiotic control groups. Immunohistochemistry showed that the positive expression of VEGF in the fresh AM group was weaker than that in the remaining three groups. MCP-1 was expressed to a similar extent in the AM-FS and fresh AM groups.

The active cytokine had high expression and stable properties at room temperature. The AM-FS cement containing 0.25 mg/ml amniotic powder can promote the repair of corneal epithelium, reduce inflammatory reaction and corneal neovascularization after alkali burning in rabbit eyes.

To investigate the impact of the iris and ciliary body morphology on the central vault after phakic posterior chamber intraocular lens (pIOL) implantation.

This research was based on the retrospective analysis of 123 patients (123 eyes) who underwent pIOL implantation in the Department of Ophthalmology, Affiliated Hospital of Qingdao University between June 2018 and June 2020. The anterior segment structure was observed with an ultrasound biomicroscope before surgery, and all morphological parameters of the iris and ciliary body were measured manually using the ImageJ software, including iris span (IS), iris convexity (IC), iris-ciliary body contact distance (ICCD) and iris-lens contact distance (ILCD). The ICCD was divided into Q1, Q2 and Q3 groups according to the equidistant distance of 0.36 mm. The lens thickness was measured with the IOLMaster. The horizontal corneal diameter and anterior chamber depth were measured using the Pentacam. The central vaults were measured by optical coherence tomography at 1 week, 3 months and 1 year after surgery. The relationships between vault values and preoperative parameters of the anterior segment were evaluated using the Pearson correlation analysis, Spearman correlation analysis, and multiple linear regression. The repeated measures ANOVA was applied to identify changes of vault values over time.

The mean values of the vaults at 1 week, 3 months and 1 year after surgery were (723±265) μm, (642±255) μm and (613±280) μm, respectively. The difference among them was statistically significant (F=50.143, P<0.001). The vaults continued to decline within 1 year after pIOL implantation, and the total decline was (122±86) μm. The vaults declined by (69±98) μm from postoperative 1 week to 3 months and by (52±54) μm from postoperative 3 months to 1 year. The regression formula showed that the pIOL size and ILCD were positively related with the vault, while the LT, IS and IC were negatively related with the vault at 1 week postoperatively (adjusted R²=0.404, P<0.001). The pIOL size and ILCD were positively related with the vault, while the IS and IC were negatively related with the vault at 3 months postoperatively (adjusted R²=0.342, P<0.001). The pIOL size was positively related with the vault, while the IS and IC were negatively related with the vault at 1 year postoperatively (adjusted R²=0.661, P<0.001). The vault values were higher in group Q3 compared to group Q1 at every timepoint, and the vault value was higher in group Q2 compared to Q1 at 1 year postoperatively.

In the early postoperative period, eyes with a larger pIOL, shorter iris span, longer contact distance between the iris and ciliary body, and longer contact distance between the iris and lens were associated with a higher rate of excessive vaults. Meanwhile, eyes with a thicker lens and larger iris reverse convexity were more likely to obtain insufficient vaults. Within one year after surgery, the pIOL size, IS, IC and ICCD continued to impact on the vault. The ICCD, ILCD and IC can reflect the posterior chamber volume and change the haptic location and force, thus affecting the vault.

The 31-year-old female patient was admitted to the General Hospital of the Chinese People′s Liberation Army for 3 days after the corneal transplantation of her right eye for 5 months.Four years ago, the patient developed red eyes, pain, dryness and photophobia after intravenous drip of cefuroxime sodium and metronidazole due to pelvic inflammation, accompanied by high fever, systemic rash and epidermal exfoliation, fingernail peeling, and mucosal ulceration in the eyes and mouth.Later, the patient received systemic hormone shock and point eye treatment in a local hospital, and the dry eyes gradually worsened. Despite continuous artificial tears and bandage mirror treatment, the corneal ulcer perforation in both eyes still occurred successively. After several penetrating keratografts and drug therapy, the ulcer and dissolution could not be prevented. He was admitted to our hospital due to corneal perforation in both eyes.Ophthalmic examination: visual acuity manual/15 cm in the right eye, intraocular pressure T-2, conjunctival sac stenosis, extensive corneal opacity and edema, ulcer about 8 mm, corneal perforation near the corneal limbus about 2 mm×5 mm below.The left eye had no light perception, a central corneal ulcer of about 8 mm, bulge of the posterior elastic layer, no anterior chamber, and atrophy of the eyeball.B-ultrasound showed choroidal detachment of the right eye.On the second day, the patient received right eye intraocular exploration, vitrectomy, ecotopic keratoscleral carrier Boston Ⅱ artificial keratoplasty, glaucoma valve implantation, autogenous ear cartilage implantation, conjunctival occlusion, and left eye lamellar keratoplasty, conjunctival occlusion.Postoperative visual acuity of right eye was -6.50 DS=0.12, intraocular pressure TN, ocular surface was stable.The left eye has no light perception and the ocular surface is stable.

The cornea is the most innervated tissue in the human body. Neuropathic pain occurring in the cornea has gradually attracted the attention of ophthalmologists. However, the definition and pathogenesis of neuropathic corneal pain (NCP) have not been clearly defined, making the diagnosis and treatment of the disease extremely challenging. In recent years, with the application of ocular surface pain assessment scales, in vivo confocal microscopy and functional magnetic resonance imaging in the clinical assessment of NCP, the diagnostic methods of NCP have been enriched. This paper reviewed the research progress of diagnostic methods of NCP, with a view to improving the ophthalmologists′ understanding of NCP and promoting the application of these technologies in the diagnosis of NCP.

Thyroid-associated ophthalmopathy is an autoimmune disease that can lead to exophthalmos, diplopia, eyelid retraction, eye movement disorders and even blindness. The main treatments include medication, radiation therapy, and surgery. Although a relatively complete treatment system has been established in clinical practice, there are still problems such as difficult treatment and easy recurrence, which seriously affect the quality of life of patients. This article summarizes the treatment status of thyroid-related ophthalmopathy in order to provide reference for clinical work.