Volume 58 · Issue 03 · 2022

This issue focuses on the research progress of pediatric ophthalmology and the diagnosis and treatment of strabismus and amblyopia. The responsible editorial committee responsible for the planning, composition and review of the key contents of this issue is Professor Zhang Wei.

With the development of science and technology, more and more new strabismus surgical procedures are introduced in the field of strabismus and pediatric ophthalmology. On one hand, these new surgical procedures improve the effect of strabismus correction and restore or rebuild binocular single vision to some extent. On the other hand, some problems associated with these surgeries have to be faced and resolved. This article review the surgical design mechanism, indications, technology, limitations, potential challenges and ways of resolution, so as to provide reference for clinicians in the processing of new strabismus surgical procedures.

Intermittent exotropia is the commonest type of strabismus, and surgery is the primary treatment. Follow-ups and other non-surgical management options can be used for patients who are younger, less cooperative, with well controlled exotropia, or unwilling to operate. However, there are many misconceptions regarding the treatment, especially the non-surgical treatment of intermittent exotropia in children, due to lack of thorough understanding about the natural course of intermittent exotropia, the timing for surgery, and the suitable candidates, effectiveness, and potential risks of different non-surgical options. This article provide an objective evaluation about the common non-surgical management options of intermittent exotropia based on the international research findings and clinical experience, in order to facilitate the correct understanding and rational use of the non-surgical treatment.

Eye examination under general anesthesia (EUA) is a key means to diagnose and treat blinding eye diseases in infants and young children. At present, domestic peers generally do not pay enough attention to EUA and are not familiar with the methods and processes of EUA. In order to better promote and standardize the examination, the Ophthalmology Group of Chinese Pediatric Society of Chinese Medical Association organized relevant domestic experts to put forward the standardized opinions on the examination of eye diseases under general anesthesia after repeated discussions, so as to provide clinicians with reference in clinical practice.

Accumulated evidence has shown that novel coronavirus disease 2019 (COVID-19) could contribute to eye disease during its pandemic, which is called COVID-19 eye disease. Currently, there is a lack of uniform and standardized guidelines for the protection of medical staff in the diagnosis and treatment process. Most ophthalmologists treat this disease according to their clinical experience. Therefore, the experts of the Public Health Ophthalmology Branch of Chinese Preventive Medicine Association have developed this consensus statement after thorough discussions, hoping to provide guiding opinions on the further prevention and control of COVID-19 eye disease in China.

To observe the effectiveness of the graded vertical rectus tenotomy procedure for small-angle vertical deviation.

Retrospective case series study. Twelve patients, including 8 males and 4 females, with an average age of (48±8) years were treated in Tianjin Eye Hospital from January 2017 to December 2019 for diplopia in primary gaze by strabismus surgery. The disease duration was (15±7) months. MRI/CT scan of the orbits and brain was performed to exclude the orbital and craniocerebral diseases. All patients underwent ocular movement examination, with the prism and alternate cover test to detect the deviation angle in primary gaze and the double Maddox test. Based on the results, the posterior segment of the nasal/temporal superior/inferior rectus muscle was operated. The changes of vertical and cyclotorsion deviation angle and the relationship between the vertical rectus graded tenotomy and corrected vertical deviation angle were observed at 1 day after surgery and the last follow-up. The vertical deviation angle was represented by M (Q₁, Q₃). Friedman test (Bonferroni correction) and linear fitting analysis were used for statistical analysis.

The follow-up time of all patients was (7±3) months. The vertical deviation angle in primary gaze before surgery [7.00 (5.25, 7.75) PD] was significantly different from that at 1 day after surgery [1.00 (1.00, 2.00) PD] and the last follow-up [1.50 (1.00, 2.00) PD] (P<0.001, P=0.003). There was no significant difference in postoperative cyclotorsion in all patients. Linear fitting results showed that 50% to 90% vertical rectus tenotomy corrected 5 to 8 PD vertical deviation (R²=0.72; P<0.001).

The graded vertical rectus tenotomy procedure can effectively improve the small-angle vertical deviation in primary gaze.

To investigate the short-term efficacy of the prism treatment in a manner of reducing prism diopters step by step for small-angle acute acquired concomitant esotropia (AACE).

Retrospective case series study. The clinical data of 17 AACE patients with strabismus ≤25 prism degrees (PD) including 6 males and 11 females, aged 14 to 60 years, who underwent the prism treatment in the Strabismus and Pediatric Ophthalmology Clinic of Shanxi Eye Hospital from October 2018 to June 2020 were collected. The prism treatment was conducted by a step-by-step reduction of prism diopters. An under-corrected prism was applied to the patient for the first time, and the degree of the prism was reduced gradually with the decrease in the degree of strabismus. Statistical analysis was performed after 6 months of treatment. The treatment success was defined as obtaining orthotropia and deleting diplopia when prism glasses were weaned off. The strabismus degree, Worth 4 dot test results, near stereopsis (Titmus stereopsis) and synoptophore fusion function before and after treatment were compared, and the factors affecting the curative effect were analyzed. Statistical methods mainly included paired t-test, Wilcoxon rank sum test, the Fisher exact test and univariate logistic regression analysis.

Among these 17 patients, 15 had myopia and 2 had emmetropia. Pretherapeutic esodeviation was (13.94±5.83) PD at near (33 cm), and was (15.76±5.24) PD at distance (6 m). After 6 months of treatment, 7 patients were successfully cured. The deviation angle at distance [(10.60±7.16) PD] and near [(9.80±6.00) PD] of the remaining 10 patients at 6 months after prismatic treatment was significantly smaller than that before treatment [(17.50±5.40) PD and (16.10±5.47) PD; t=3.69, 4.10; both P<0.01]. The Titmus stereogram showed that 2 cases had no stereopsis, 6 cases had peripheral stereopsis, 3 cases had macular stereopsis, and 6 cases had foveal stereopsis before treatment. Stereopsis was significantly improved at 6 months after prismatic treatment, with 3 cases havimg macular stereopsis and 14 cases having foveal stereopsis (Z=-2.99; P<0.01). The Worth-4-dot test disclosed that, the number of patients who saw four lamps at distance and near was 0 and 2 before treatment, and 7 and 9 after treatment, respectively, and the difference was statistically significant (both P<0.05). The divergent fusional amplitude and convergent fusional amplitude in the synoptophore at 6 month after treatment was not significantly different from that before treatment (both P>0.05). The efficacy of treatment was not significantly related to the duration from onset to treatment, the pretherapeutic esodeviation, the Titmus stereoacuity, cycloplegic refractive error, and age (all P>0.05). None of the 7 patients, who were successfully cured had a recurrence of esotropia or diplopia during the observation period of 6 to 24 months (median, 11 months).

Prism treatment in a manner of step-by-step reduction of prism diopters can significantly diminish the degree of esotropia and improve the binocular function in small-angle AACE. Furthermore, some patients could be cured, achieving orthophoria without diplopia.

To explore the feasibility of applying machine-learning hierarchical clustering algorithm to waveform-type automatic classification and diagnosis in congenital nystagmus (CN).

A retrospective case series study. A total of 90 patients (90 eyes) diagnosed with CN at Tianjin Eye Hospital from December 2018 to September 2019 were included in the study, including 67 males and 23 females, aged (12±9) years old. Eye movement waveforms were recorded with the video eye tracker in all patients. Analyses with unsupervised machine-learning hierarchical clustering algorithm were performed on the normalized eye movement waveforms. The visualized clustering results were obtained for further waveform naming. The occurrence rate of each waveform type was calculated, and the correlation between the proportion of each waveform type and the visual function of CN patients was analyzed. Independent sample t-test and Pearson correlation analysis were used for statistical analysis.

The 46 620 cycles of validated waveforms from the 90 CN patients were categorized into 7 types of waveforms through machine-learning hierarchical clustering algorithm, named type Ⅰ, type Ⅱ, type Ⅲ, and types Ⅳ_1-4, respectively. In the 46 620 cycles of eye movement waveforms from the 90 patients with CN, there were 14 259 cycles of type Ⅰ (30.59%), 11 498 cycles of type Ⅱ (24.66%), 4 083 cycles of type Ⅲ (8.76%), 5 430 cycles of type Ⅳ₁ (11.65%), 3 451 cycles of type Ⅳ₂ (7.40%), 3 015 cycles of type Ⅳ₃ (6.47%), 2 663 cycles of type Ⅳ₄ (5.71%) and 2 221 cycles of unclassified waveforms (4.76%). The waveforms of types Ⅰ, Ⅱ and Ⅲ corresponded to the 3 basic CN eye movement waveforms (velocity-increasing jerk waveform, velocity-decreasing jerk waveform and pendular waveform) described in the textbooks, and the waveforms of types Ⅳ_1-4 were complex waveforms. The proportions of patients with the 7 types of waveforms were 78.89% (71 cases), 41.11% (37 cases), 17.78% (16 cases), 20.00% (18 cases), 7.78% (7 cases), 15.56% (14 cases) and 11.11% (10 cases), respectively. According to the results of automatic classification, 38 (42.22%) CN patients presented with only one type of waveforms, and the remaining 52 (57.78%) CN patients presented with two or more types of waveforms, including 23 (25.56%) patients with 3 or more types of waveforms and 5 (5.56%) patients with 4 types of waveforms. The proportions of type Ⅰ component were significantly correlated with the patients′ best corrected visual acuities (BCVAs;logarithm of the minimum angle of resolution) (r=-0.39; P<0.01), and there was no relationship between the proportions of type Ⅱ component and the patients′ BCVAs (P>0.05). The BCVAs of the patients with type Ⅰ as the dominant component were better than those of the patients with type Ⅱ as the dominant component, with statistically significant difference (0.19±0.14 vs. 0.45±0.37;t=2.77; P<0.05).

Machine-learning hierarchical clustering algorithm can be used for waveform-type automatic classification and discrimination in CN and provide an auxiliary method for the precise diagnosis and evaluation of the disease.

To investigate the changes of the microstructure and vascular density in the superficial retinal layer of buried optic disc drusen (ODD) patients.

Retrospective case-control study. A total of 36 ODD eyes (20 patients) and 26 normal control eyes were recruited in Beijing Union Medical College Hospital from January 2018 to July 2020. Measurement of best corrected visual acuity (BCVA), intraocular pressure, slit lamp, fundus examination and visual field examination were performed. The images and data of spectral domain-optical coherence tomography (SD-OCT) and optical coherence tomography angiography (OCTA) were analyzed and summarized. The differences of nasal retinal nerve fiber layer (RNFL), ganglion cell complex (GCC) thickness and macular superficial vascular density (VD) between ODD patients and normal controls were compared by independent sample t-test or Mann Whitney U test (the right eye was selected in bilateral ODD patients).

The 20 ODD patients and 26 normal controls were all female. There was no significant difference in age between the two groups (P>0.05). The BCVA and visual field examination was normal in all ODD patients. The SD-OCT examination showed an oval low signal shadow under the nasal outer nuclear layer of the optic disc, or local accumulation like a medium signal shadow with a clear boundary, and a high signal capsule in ODD patients. The RNFL in the upper nasal side of the ODD group was significantly different from the normal control group [(102.6±19.1) μm vs. (119.0±13.8) μm; t=-2.81; P<0.01]. Compared with normal control group [101.0 (100.0, 102.0) μm], the average GCC thickness in the ODD group [97.0 (89.3, 99.8) μm] was significantly different (U=48.50; P<0.01). The OCTA en-face scan showed that the vascular network in the macular area of the affected eyes was sparser than that of the control eyes. There was significant difference in superficial macular VD beteeen the ODD group (48.5%±2.8%) and the control group (51.0%±2.3%) (t=-2.63; P<0.05).

There is thinning in the RNFL upper nasal side and GCC layer of the macular region in buried ODD patients, and the superficial VD of the macular region in buried ODD patients is lower than that in the normal controls.

To screen the differently expressed microRNAs (miRNAs) and to explore the effect and mechanism of microRNA-3907 (miR-3907) in meibomian gland carcinoma (MGC).

Experimental research. MGC tissues and para-carcinoma tissues of patients diagnosed with MGC by histopathology were collected from July 2011 to January 2019 in Tianjin Medical University Eye Hospital. The miRNA microarray analysis of MGC and para-carcinoma tissue samples from 5 patients was performed. miR-3907 with a significant up-regulation was selected as a research object. Bioinformatics predicted and dual-luciferase gene reporter assay verified miR-3907 target genes. The protein expression levels of target genes in 18 MGC tissues and 6 para-carcinoma tissue samples were determined by immunohistochemical staining. miR-3907 over-expression, miR-3907 knock-down, target gene knock-down and miR-3907 knock-down with target gene knock-down were respectively performed in MGC cell. The mRNA and protein expressions were validated by real-time PCR and Western blotting after transfection. The cell proliferation and migration ability was detected by cell counting kit-8 and scratch experiment after transfection. The main statistical methods were Fisher′s exact test, independent sample t test, two-factor repeated measure analysis of variance.

There were 22 differently up-regulated miRNAs and 5 differently down-regulated miRNAs in MGC tissues, of which miR-3907 was significantly up-regulated. Thrombospondin-1 (THBS1) was a target gene of miR-3907 according to bioinformatics and dual-luciferase gene reporter assay. The positive expression rate of THBS1 protein in para-carcinoma tissues (6/6) was significantly higher than that in MGC tissues (5/18), and the difference was statistically significant (P=0.003). Compared with the negative control group, the proliferation ability of the miR-3907 over-expression group was increased at 48 h and 72 h (F=3.70, 2.65; both P<0.01), and the migration rate at 24 h was significantly higher (54.6%±3.4% vs. 34.2%±0.6%; t=8.34, P<0.01). Compared with the negative control group, the proliferation ability of the miR-3907 knock-down group was decreased at 24 h, 48 h and 72 h (F=3.10, 2.17, 3.09; all P<0.05), and the migration rate at 24 h was significantly lower (40.8%±2.8% vs. 69.7%±2.7%; t=10.42, P<0.01). Compared with the negative control group, the THBS1 knock-down group promoted cell proliferation at 24 h, 48 h and 72 h (F=3.84, 3.79, 2.24; all P<0.05), and the migration rate at 24 h was significantly increased (82.5%±1.9% vs. 37.6%±5.1%; t=11.74, P<0.01). Compared with the control group, the miR-3907 knock-down with THBS1 knock-down group increased proliferation at 24 h and 48 h (F=3.97, 3.31; both P<0.05), and the migration healing rate at 24 h was significantly increased (56.9%±2.2% vs. 41.9%±4.3%; t=3.53, P<0.05).

There are differently expressed miRNAs between MGC and para-carcinoma tissues, which may be related to the occurrence and development of MGC. miR-3907 in MGC tissues has a significant difference from that in para-carcinoma tissues. Moreover, miR-3907 can play a role in promoting proliferation and migration of MGC by inhibiting the expression of THBS1.

The proband presented with bilateral congenital non-progressive ptosis and limitation of eye rotation since childhood. The diagnosis was congenital fibrosis of the extraocular muscles. A new KIF21 pathogenic mutation locus was found. It was a KIF21A-ex20 c.2821C>T (p.Arg941Trp) heterozygous missense mutation, which caused the disease in this family.

A female patient presented with redness and visual acuity loss in the left eye for more than 4 months. Ophthalmic examination revealed a large number of gray-white masses and lesions with fuzzy boundaries on the iris surface. Retinoblastoma was diagnosed after enucleation.

An age-related cataract patient who underwent femtosecond laser intrastromal keratotomy in the right eye for presbyopia correction 8 years ago was subjected to femtosecond laser-assisted phacoemulsification, with implantation of a monofocal intraocular lens (IOL) and a trifocal IOL in the right and left eyes, respectively. The corneal stromal ring was complementary to the monofocal IOL, which recovered the distance and near visual acuity, in the right eye postoperatively. The trifocal IOL provided good intermediate visual acuity for the left eye. The vision of the patient reached an ideal level for all visual distances. The binocular fusion was within the normal range, and the stereoscopic vision was restored. We hope that this case report can act as a reference for the treatment of cataract after presbyopia corrective surgery.

Acute acquired concomitant esotropia (AACE) is a special type of esotropia that occurs suddenly and is accompanied by diplopia. In recent years, the number of patients with this eye disease has increased significantly. With differences in age and refractive status, children and adults have their own characteristics in terms of AACE classification, refractive status, eye position, and binocular visual function. However, the pathogenesis of AACE is still unclear. This article explores the pathogenesis and risk factors of AACE, including refractive error, convergence spasm, extraocular muscle, and visual cortex, that may be involved. The authors recommend that AACE, which is not related to intracranial and systemic diseases, should be classified according to the dominant mechanism of the disease.

With the continuous development of imaging technology, high-resolution magnetic resonance imaging (MRI) can be used to quantitatively analyze the morphological and functional status of orbital soft tissue. Changes in the morphology and function of the extraocular muscles and pulleys may be the mechanical basis of some incomitant and special patterns of strabismus. Recent MRI research advances related to the characteristics of extraocular muscles and pulleys of healthy people and strabismic patients are reviewed in this article.

Multiple sclerosis (MS) is an inflammatory reactive autoimmune disease characterized by diffuse axonal degeneration of the central nervous system. The exact etiology and pathogenesis remain unclear. Optical coherence tomography angiography is a new technology of angiography, which can obtain the images of each layer of blood vessels in the scanning area. It is non-invasive, fast and quantifiable. Observation of retinal vasculopathy may assist in the evaluation of brain diseases. This article reviews the previous research results at home and abroad of ocular blood flow changes observed by optical coherence tomography angiography in MS in recent years, in order to provide reference for the study of the underlying pathogenesis of MS and clinical evaluation.

Myopia is a high incidence in China, and the incidence tends to be younger. The severity of children's vision health protection is becoming increasingly prominent. The development of refractive state of human eye is a process involved by many factors, and the refractive characteristics of infants and young children are quite different than those of adults. This paper focuses on the natural progress of the development of refractive state in infants and children, and analyzes the main characteristics and functions of the changes of ocular refractive elements.