Volume 55 · Issue 05 · 2019

This issue focuses on the research progress of glaucoma diagnosis and treatment. Professor Wang Ningli is the responsible editorial committee responsible for the planning, composition and review of the key contents of this issue.

The childhood glaucoma presents high blindness and requires high quality of surgical treatment, laying heavy burdens on patients′ families and the society. So far, there is no widely accepted standard and consensus on the surgical treatment for childhood glaucoma. Angle surgery and trabeculotomy, especially microcatheter-assisted circumferential trabeculotomy, have a good therapeutic effect on childhood glaucoma. Established consensus and popularization of the new surgery can significantly improve the success rate of treatment for childhood glaucoma. (Chin J Ophthalmol, 2019, 55: 321-324)

Primary angle closure glaucoma (PACG) is a common clinical disease, and recent research has made new progress. Therefore, the Glaucoma Group of Ophthalmology Branch of Chinese Medical Association, based on evidence-based ophthalmology medicine, reached a further consensus on the classification system, diagnostic methods and treatment principles of PACG in China for clinicians' reference.(Chinese Journal of Ophthalmology, 2019, 55:325-328)

Current research results show that the prevalence of normal intraocular pressure glaucoma (NTG) in China reaches 1.0%, and improper division of normal intraocular pressure can easily lead to misdiagnosis. The Glaucoma Group of Ophthalmology Branch of Chinese Medical Association synthesized the research progress and achievements of NTG in recent years, and reached a further consensus on the diagnosis and treatment principles of NTG in China based on evidence-based ophthalmology medicine, so that clinicians can refer to it when diagnosing and treating glaucoma.(Chinese Journal of Ophthalmology, 2019, 55:329-332)

As an irreversible blinding eye disease, early diagnosis and intervention of glaucoma is of great significance. Because primary open-angle glaucoma is mainly characterized by optic nerve and visual function damage, coherence light tomography (OCT) and standardized automatic visual field examination (SAP) are often used as auxiliary diagnostic methods in clinic. This paper expounds the pathogenesis and objectivity of the examination, and proposes that the results of OCT can replace the results of SAP as a new index for the diagnosis and follow-up of glaucoma.(Chinese Journal of Ophthalmology, 2019, 55:333-334)

The key of clinical diagnosis and treatment of glaucoma is the diagnosis and progress monitoring of the disease. The clinical diagnosis and management of glaucoma can only rely on the existing means to detect the changes of its structure and function. Visual field examination of glaucoma has high sensitivity, specificity and high reproducibility, so it has always been considered as the gold standard for diagnosing and evaluating the progression of glaucoma. However, with the development of science and technology, the structural detection methods represented by coherence light tomography (OCT) show many advantages. Some scholars believe that OCT can replace visual field examination as a new index for glaucoma diagnosis and follow-up. According to this point of view, from the different characteristics of structural and functional detection, the existing problems of OCT detection and its disadvantages compared with visual field examination, this paper illustrates that OCT does not have the ability to replace visual field examination at present stage, and the continuously improved visual field examination is still an irreplaceable standard for glaucoma diagnosis and follow-up management.(Chinese Journal of Ophthalmology, 2019, 55:335-337)

To investigate the relationship between the spontaneous focal lamina cribrosa (LC) defect and the progression of visual field defect (VFD) in primary open-angle glaucoma (POAG).

Case-control study. The patients who were diagnosed as POAG with at least 5 visual field results had been collected from June 2018 to January 2019 at Beijing Tongren Hospital Affiliated to Capital Medical University. Serial imaging by swept source optical coherence tomography B-Scan of the optic discs were acquired at the end of the follow-up and LC defects status were reviewed. Intraocular pressure, mean defects of visual field, central corneal thickness and axis length were recorded in the follow-up duration. Eyes were classified as having either progressive or nonprogressive VFD, and associating factors were evaluated by χ ² or Fisher′s test, mixed-effect model analysis and multivariate Logistical regression analysis.

A total of 32 subjects (64 eyes) were enrolled in the study with mean age of (47±14) years, the group consisted of 17 males and 15 females. Fourty-five eyes showed nonprogressive VFD. LC defects were more common in eyes without (28/45) rather than with progressive VFD (5/19) (χ²=6.896, P=0.009). Eyes with nonprogressive VFD showed longer axis length[(26.82±1.34) mm vs. (25.79±1.44) mm; t=6.589, P=0.013] and wider LC defects diameter[211 (165-326) μm vs. 114 (106-156) μm; Z=4.797, P=0.042]. Multivariate Logistic regression analysis revealed that the presence of LC defect was significantly associated with nonprogressive VFD (odds ratio=0.217, P=0.012). There were 7 subjects with asymmetry VFD and the incedence of LC defects without progression (7/7) is higher than fellow eye with progression (1/7, P=0.002). There was only one patient with progressive VFD showed one LC defect with an smaller diameter (169 μm) than that in the contralateral eyes with stable VFD (269 μm).

LC defects are more common in eyes with nonprogressive VFD. Spontaneous LC defects are associated with nonprogressive glaucomatous defects and could be a protective factor for POAG. (Chin J Ophthalmol, 2019, 55:338-346)

To evaluate the outcomes of trabeculectomy combined with a new prophylactic sclerotomy in late stage juvenile open angle glaucoma (JOAG) and primary congenital glaucoma (PCG) patients at high risks of intraoperative and postoperative suprachoroidal hemorrhage (SCH).

A retrospective case series study. Thirty-three eyes of 28 JOAG patients and 15 eyes of 12 PCG patients with high risk factors for severe choroidal effusion or SCH were enrolled from November 2006 to April 2012 at Eye and ENT Hospital of Fudan University. The standard trabeculectomy accompanied by prophylactic sclerotomy was performed (video attached). Ophthalmic examinations were performed before and after the surgery. Surgical outcome was assessed in terms of intraocular pressure (IOP), best-corrected visual acuity, optic nerve head cup disc ratio, visual field, and complications. All patients were followed up for at least 1 year. Complete success was defined as an IOP ≥6 mmHg (1 mmHg=0.133 kPa) but ≤18 mmHg without medication. Qualified success was defined as an IOP ≥6 mmHg but ≤18 mmHg with local application of medications. Kaplan-Meier survival curves were drawn for the success rate calculation.

The mean age of all 40 patients was (13.2±9.4) years old. And among them, 22 patients were male and 18 patients were female. The mean follow-up time was (31.8±15.9) months. At the postoperative 3^rd year, the complete success rate was 75.8%, and the qualified success rate was 90.0%. In our case series, one eye had expulsive SCH intraoperatively and two eyes had delayed SCH postoperatively. All of them were successfully saved without further surgery and with no significant damage to visual function.

Trabeculectomy combined with prophylactic sclerotomy is a promising technique developed to control IOP in late stage JOAG and PCG patients, which provides a potential intervention to reduce severe consequences of massive choroidal effusion or SCH. (Chin J Ophthalmol, 2019, 55: 347-354)

To investigate the expression of microRNA-1 (miR-1) and its regulatory function on fibronectin (FN) in human trabecular meshwork cells (HTMC) under oxidative stress.

Experimental study. After HTMC were treated with 0, 60, 100, 200, 400 μmol/L hydrogen peroxide (H ₂O₂) for 6 h, respectively, the cells were placed in culture medium for 24 h. The expression of miR-1 and FN mRNA in these cells were detected by real-time quantitative PCR. According to bioinformatics analysis, the target gene of miR-1 is predicted to be FN; pcDNA3/pri-miR-1 vectors, pcDNA3/enhanced green fluorescent protein (EGFP)-FN-3'UTR vectors and pcDNA3/EGFP-FN-3'UTRmut vectors were constructed. pcDNA3/pri-miR-1 were co-transfected with pcDNA3/EGFP-FN-3'UTR or pcDNA3/EGFP-FN-3'UTRmut respectively into HTMC. pDsRed2-N1 was taken as internal reference. After 48 h transfection, the absorbance of EGFP and red fluorescent protein (REP) was detected with fluorescence spectrophotometer to explore the effect of miR-1 on FN expression. HTMC was stimulated with 200 μmol/L H₂O₂ for 24 h after overexpression plasmid of miR-1 was transfected into it, and then FN mRNA and protein levels were detected via real time PCR, Western blotting and immunofluorescence. Data were analyzed via one-way analysis of variance or t test.

With the increase of H₂O₂ concentration, miR-1 decreased (F=390.80, P<0.01) while FN increased (F=13.16, P<0.01). The level of miR-1 in HTMC stimulated by 200 μmol/L and 400 μmol/L H ₂O₂ decreased to 0.608±0.014 (t=21.67, P<0.01) and 0.409±0.020 (t=29.91, P<0.01), respectively, compared with untreated control cells (1.000); whereas, the mRNA levels of FN increased to 1.630±0.233 (t=4.47, P=0.011) and 1.903±0.246 (t=6.15, P=0.003), respectively, compared with untreated control cells(1.000). Through bioinformatics analysis, miR-1 might have candidate binding site in FN mRNA 3'-UTR. Meanwhile, these cells co-transfected with pcDNA3/pri-miR-1 and pcDNA3/EGFP-FN-3'UTRmut (0.562±0.018) had higher EGFP expression than cells co-transfected with pcDNA3/pri-miR-1 and pcDNA3/EGFP-FN-3'UTR (0.329±0.015) (t=17.39, P<0.01). Compared with the control (1.000), after overexpressing miR-1 the mRNA expression and the protein level of FN decreased to 0.294±0.081 (t=11.01, P<0.01) and 0.584±0.022 (t=5.57, P<0.01), respectively.

MiR-1 decreases while FN increased in HTMC under oxidative stress. MiR-1 inhibits FN expression through targeting FN 3'-UTR.(Chin J Ophthalmol, 2019, 55: 355-360)

To explore the imaging features of patients with special forms of strabismus and summarize the subtypes by using MRI imaging techniques.

A retrospective case series study. Among the patients who visited the Beijing Tongren Hospital between 2006 and 2016, 1 113 patients were identified with special forms of strabismus after complete ophthalmic and orthoptic evaluations. These patients were further evaluated using several types of high-resolution MRI techniques of the oculomotor nerves in the brain, the cavernous sinus, and the orbits.

Among the 1 113 patients, 818 patients (73.5%) were identified with MRI abnormal conditions, and 295 patients (26.5%) were identified with MRI normal conditions. Nine different disease types were identified in the studied populations, which included 257 patients (23.1%) with congenital cranial dysinnervation disorders, 209 patients (18.8%) with thyroid associated ophthalmopathy, and 169 patients (15.2%) with abnormalities of the extraocular muscles. Other diseases included orbital fractures (3.3%, 37 patients), intraorbital inflammations (2.7%, 30 patients), tumors (2.3%, 26 patients), injuries of medial rectus muscle after endoscopic sinus surgery (1.2%,13 patients), and lesions of cavernous sinus (2.0%, 22 patients). Additional 55 patients (4.9%) were identified with other causes such as high myopia fixed esotropia, and so on.

Summarizing the common clinical characteristics and rules with the help of MRI can further clarify the etiology of special forms of strabismus, and accurately guide the diagnosis and treatment of strabismus. (Chin J Ophthalmol, 2019, 55: 361-368)

To summarize and analyze the clinical manifestation of conjunctival papilloma, its relationship with human papillomavirus (HPV) infection and the recurrence after the combination of operation and pharmacotherapy.

A retrospective case series study. Analysis of 40 patients (41 eyes) with conjunctival papilloma treated at Peking Union Medical College Hospital from January 2008 to June 2018 was performed. All patients were given routine blood and urine, hepatitis B virus surface antigen, antibodies to hepatitis C virus, antibodies to human immunodeficiency virus and antibodies to Treponema pallidum testing, and HPV testing for the urethra epithelial tissue. Direct contact of the tumor with instruments was avoided during surgery, and freezing treatment was combined. HPV testing was performed for the resected conjunctival papilloma. Multiple medications were used after surgery.

In 40 cases with 41 eyes, there were 22 males (23 eyes) and 18 females (18 eyes). A single tumor was seen in 27 eyes, and multiple tumors were seen in 14 eyes. Thirteen patients (13 eyes) older than 50 years old had pedicel-free papillpma, and 27 patients (28 eyes) aged from 12 to 40 years had pedicel-type papillpma. All cases were confirmed by pathology as conjunctival papilloma, of which 9 cases showed moderate to severe atypical hyperplasia on squamous cells. The HPV test was positive in 17 out of the 40 cases (42.5%) of conjunctival papilloma. Urine test results of 16 patients (40.0%) were positive for occult blood and showed that urinary white blood cell was elevated. Of the 40 patients, 33 were newly diagnosed and 7 had a relapse. The average follow-up time was (37.4±11.9) months after combined therapy and no recurrence was found in any patients.

Conjunctival papilloma is usually observed in people aged from 20 to 40 years and older than 50 years, and it often occurs in one eye. Its main pathological feature is benign tumors of the papillary hyperplasia on the conjunctival epithelial tissue. Some patients have atypical hyperplasia of squamous cells. The cause of the disease may be related to the infection of HPV and the urinary tract. Combined treatment can reduce the recurrence rate of conjunctival papilloma. (Chin J Ophthalmol, 2019, 55: 369-373)

To evaluate the clinicopathological features of ocular natural killer(NK)/T cell lymphoma.

Data of 21 patients (22 eyes) with ocular NK/T cell lymphoma treated at Eye & ENT Hospital of Fudan University from January 2006 to March 2018 were retrospectively analyzed for clinical data, morphology, immunophenotype and outcomes.

There were 10 males and 11 females with ages from 3 to 77 years (mean, 43 years). There were 20 unilateral cases (10 left eyes and 10 right eyes) and 1 bilateral case. Except for 1 case of corneal perforation resulting from the involvement of the conjunctiva and cornea, the other cases all involved the orbit (including eyelids and conjunctiva) as demonstrated by radiologic studies, with the lacrimal sac involved in 3 cases, and the nasal cavity or maxillary sinus involved in 2 cases. Three patients had been previously diagnosed sinonasal NK/T cell lymphoma with radiotherapy and chemotherapy. Two patients had a history of ovarian NK/T cell lymphoma with chemotherapy. One patient had multiple ulcers of skin and mucosa at presentation. There were 13 primary ocular NK/T cell lymphomas without evidence of nasal or systemic involvement. All patients presented with eyelid swelling and decreased visual acuity. There were proptosis in 18 cases, motility restriction in 13 cases, eyelid ulceration in 3 cases, and fever in 4 cases. They had all been previously diagnosed as orbital pseudotumor or cellulitis and there was no response to steroids and antibiotics. Pathological examination showed atypical lymphoid infiltration with an angioinvasive growth pattern causing coagulative necrosis. Cytologically, the medium-sized neoplastic cells showed irregular folded nuclei. The neoplastic cells were positive for cytoplasmic CD3ε, CD56, and cytotoxic molecules and Epstein-Barr virus-encoded RNA (EBER) in situ hybridization. Seven patients were lost to follow-up. Ten patients died 2.0 to 17.0 months after diagnosis (mean, 6.3 months) despite treatment with chemotherapy and radiotherapy.

Ocular NK/T cell lymphoma is a rare form of ocular lymphoma. There are primary NK/T cell lymphoma and secondary ocular NK/T cell lymphoma with nasal or systemic involvement. The rarity of this tumor and inflammatory signs make it challenging to identify these tumors early. The neoplastic cells are positive for cytoplasmic CD3ε, CD56, cytotoxic molecules and EBER in situ hybridization. Despite aggressive therapy, it demonstrates high lethality with poor prognosis.(Chin J Ophthalmol, 2019, 55: 374-380)

To investigate the clinical, imaging and pathological features of adult onset xanthogranuloma.

Retrospective case series study.The clinical data of 4 adult patients with adult onset xanthogranuloma treated in the Tianjin Medical University Eye Hospital from 2015 to 2017 were analyzed.

There were 1 male and 3 females, aged 46-73 years, with an average age of 55 years. The duration of eyelid swelling was from 6 months to 6 years. One case was binocular and 3 cases were monocular. There were progressive enlargement of eyelid swelling and subcutaneous cord nodules with poor mobility and no tenderness in all 5 eyes. The eyelid skin in 2 patients (2 eyes) was bulging and yellow. CT examination showed swelling of the eyelids and soft tissue thickening in 5 eyes. There were lacrimal gland enlargement in 3 eyes, upper rectus muscle involvement in 3 eyes, external rectus muscle involvement in 1 eye, lower rectus muscle involvement in 1 eye, superior oblique muscle involvement in 1 eye, and involvement of both the superior and inferior rectus muscles in 1 eye. In 1 patient (1 eye), the lesion showed low and medium signals on T₁ weighted images and T₂ weighted images. Three patients (4 eyes) underwent color Doppler ultrasonography, showing the echo zone in the irregularly shaped eyelid was strong, the internal echo was uneven, the local echo was low, and the boundary was not clear. One of the eyes showed a blood flow signal. All patients underwent surgical resection. The pathological results showed infiltration of foamy tissue cells, Touton cells, lymphocytes and plasma cells. Immunohistochemistry demonstrated 3 patients (4 eyes) expressed CD68, and 1 patient (1 eye) expressed S-100. After 6 months to 2 years of follow-up, 3 patients had no recurrence. One patient developed eye discomfort at 6 months after surgery, and the symptoms were relieved after treatment with triamcinolone.

Adult onset xanthogranuloma mainly manifest as eyelid swelling, periorbital mass and skin color changes, generally with no systemic involvement. Imaging examination mainly shows the involvement of soft tissues, lacrimal glands and muscles around the eyelids. The main features of the pathology are infiltration of foamy tissue cells, Touton giant cells, lymphocytes and plasma cells. (Chin J Ophthalmol, 2019, 55: 381-386)

One patient complaining of blurred vision in the right eye with visual fatigue for more than 1 month went to the ophthalmology department. He had a history of high myopia in both eyes for more than 20 years. Binocular high myopia with paradiscal choroidal cavity was diagnosed by visual acuity, fundus, enhanced depth scanning mode coherence light tomography, en face coherence light tomography, coherence light tomography angiography and standard automatic visual field examination.(Chinese Journal of Ophthalmology, 2019, 55:387-389)

Wang Ningli, Chief Physician, Prof. Director of Beijing Tongren Ophthalmology Center, Beijing Tongren Hospital affiliated to Capital Medical University, and Dean of College of Ophthalmology, Capital Medical University. Former chairman of the Ophthalmology Branch of Chinese Medical Association and leader of the Glaucoma Group, president of the Ophthalmologist Branch of Chinese Medical Doctors Association, chairman of the Public Health Ophthalmology Branch of Chinese Preventive Medicine Association, and leader of the National Blindness Prevention Technical Guidance Group; Honorary Editor-in-Chief of the Editorial Board of Chinese Journal of Ophthalmology; Fellow of the International Academy of Ophthalmology, President of the Asia-Pacific Ophthalmology Society, Member of the Board of Directors of the World Glaucoma Association, and Member of the Board of Directors of the Asia-Pacific Glaucoma Association.

The patient was a 45-year-old male. Due to the loss of vision in his left eye for 1 month, he went to the Department of Ophthalmology of Dushanzi People's Hospital. Primary open-angle glaucoma was previously diagnosed. After surgical treatment in an external hospital 5 years ago, intraocular pressure fluctuated between 15 and 30 mmHg (1 mmHg =0.133 kPa); Deny history of hypertension, diabetes, blood diseases, eye trauma and myopia. The whole body examination showed no abnormalities. Eye examination: the visual acuity was 0.05 in the right eye and 0.12 in the left eye, both of which could not be corrected; The conjunctival filter vesicles above both eyes were flat and diffused, and peripheral incision holes were seen in the iris at 12: 00, and no other abnormalities were seen in the anterior segment. For fundus examination, seeQuintessence Picture 1。 Fluorescein fundus angiography examination is shown inQuintessence Picture 2。 Clinical diagnosis: primary open-angle glaucoma in both eyes; Collateral circulation formation of retinal vein occlusion in the left eye.

Optical coherence tomography angiography (OCTA) can reflect the vascular morphological changes of various types of uveitis, including flow void, hypoperfusion, capillary abnormalities, capillary network disorders and choroidal neovascularization. Moreover, OCTA is featured of particular quantification functions, such as measurement of the areas of foveal avascular zone, choroidal neovascularization, vascular density and flow index. Despite certain limitations, its characteristics of non-invasiveness and capabilities of depicting vascular details are helpful to the observation and follow-up of uveitis. As current interpretation of the OCTA images for uveitis is not thorough enough, hence further analysis of the images is needed to improve its application on uveitis. (Chin J Ophthalmol, 2019, 55: 392-396)

Since the 21st century, new non-filter vesicle-dependent anti-glaucoma surgery has been emerging in clinic. The mechanism is to reduce intraocular pressure by reducing the resistance of aqueous humor outflow physiological pathway. The only difference lies in the operation site and the use method. In this paper, the anti-glaucoma surgery based on the physiological pathway of aqueous humor outflow is classified according to its action site, and its mechanism and indication are discussed, so as to provide reference for clinicians.(Chinese Journal of Ophthalmology, 2019, 55:397-400)