Jian-Feng He

Increased microRNA-155 and decreased microRNA-146a may promote ocular inflammation and proliferation in Graves’ ophthalmopathy

Graves’ ophthalmopathy is an inflammatory autoimmune disease of the orbit, characterized by inflammation and proliferation of the orbital tissue caused by CD4+T cells and orbital fibroblasts. Despite recent substantial findings regarding its cellular and molecular foundations, the pathogenesis of Graves’ ophthalmopathy remains unclear. Accumulating data suggest that microRNAs play important roles in the pathophysiology of autoimmunity and proliferation. Specifically, microRNA-155 (miR-155) can promote autoimmune inflammation by enhancing inflammatory T cell development. In contrast to miR-155, microRNA-146a (miR-146a) can inhibit the immune response by suppressing T cell activation. Furthermore, miR-155 and miR-146a are involved in cell proliferation, differentiation, and many other life processes. Thus, miR-155 and miR-146a, with opposite impacts on inflammatory responses carried out by T lymphocytes, appear to have multiple targets in the pathogenesis of Graves’ ophthalmopathy. Our previous work showed that the expression of miR-146a was significantly decreased in peripheral blood mononuclear cells from Graves’ ophthalmopathy patients compared with normal subjects. Accordingly, we proposed that the expression of miR-155 increased and the expression of miR-146a decreased in the target cells (CD4+T cells and orbital fibroblasts), thus promoting ocular inflammation and proliferation in Graves’ ophthalmopathy. The proposed hypothesis warrants further investigation of the function of the differentially expressed microRNAs, which may shed new light on the pathogenesis of Graves’ ophthalmopathy and lead to new strategies for its management.

Risk Factors for Idiopathic Optic Neuritis Recurrence

Background Approximately 30–50% of idiopathic optic neuritis (ION) patients experience one or multiple episodes of recurrence. The aim of this study was to search for risk factors for ION recurrence. Methods Clinical data on hospitalized patients diagnosed with ION between January 2003 and January 2011 at the First Affiliated Hospital of Guangxi Medical University were retrospectively collected. Univariate and multivariate analyses were performed on factors that might cause ION recurrence. In total, 115 ION cases (32 recurrent and 83 non-recurrent cases) with complete data were analyzed. The length of the follow-up period ranged from 12 to 108 months (median: 42 months). Results The univariate analysis showed that the recurrence rate for unilateral ION was higher than that for bilateral ION (40% vs. 12%, p = 0.001). Underlying diseases had a significant impact on recurrence (p<0.001): the recurrence rates due to neuromyelitis optica (NMO), multiple sclerosis (MS), demyelinating lesions alone of the central nervous system, and unknown causes were 89%, 70%, 41%, and 8.7%, respectively. The multivariate analysis showed that the factors causing relatively high recurrence rates included NMO (odds ratio [OR], 73.5; 95% confidence interval [CI], 7.3 to 740.9), MS (OR, 33.9; 95% CI, 5.2 to 222.2), and demyelinating lesions alone (OR, 8.9; 95% CI, 2.3 to 34.4), unilateral involvement (OR, 5.7; 95% CI, 1.5 to 21.3), relatively low initial glucocorticoid dosage (equivalent to ≤100 mg prednisone/day) (OR, 4.3; 95% CI, 1.0 to 17.9). Conclusion Underlying diseases, laterality (unilateral or bilateral), and initial glucocorticoid dosage are important risk factors of ION recurrence. Clinical physicians are advised to treat ION patients with a sufficient dose of glucocorticoid in the initial treatment stage to reduce the recurrence risk.

Gypenosides might have neuroprotective and immunomodulatory effects on optic neuritis

Optic neuritis is a common disease in young adults, inducing apoptosis of retinal ganglion cells, which leads to varying degree of visual function damages, even blindness. As the standard treatment, methylprednisolone pulse therapy can only promote the recovery of visual acuity but not prevent retinal ganglion cell degeneration. It cannot help improve the ultimate visual outcome. Both inflammatory response and endogenous oxidative stress play crucial roles in the progression of optic neuritis. The combination of immunomodulatory and antioxidant is expected to improve the prognosis of the disease by preventing the apoptosis of retinal ganglion cells. Triterpenoids (oleanolic acid derived) were reported to have the dual capacity of simultaneously repressing production of pro-inflammatory mediators and exerting neuroprotective effects through induction of anti-oxidant genes in experimental optic neuritis. Gypenosides with an aglycone mainly of dammarane-type tetracyclic triterpenoids, also has the dual capacity of immune regulation and antioxidation. Both gypenosides and oleanolic acid were reported to have similar roles in hepatoprotection. Beside, gypenosides were reported to have the capacity of modulating the activation of immune cells and the expression of cytokines. In addition, gypenosides showed neuroprotective effect against oxidative injury in dopaminergic neurons and mouse model of Parkinsons disease. Accordingly, we propose that gypenosides have potential neuroprotective and immunomodulatory effects on optic neuritis through antioxidation and immune regulation. The application of gypenosides might prevent the apoptosis of retinal ganglion cells and improve the ultimate visual outcome in patients with optic neuritis.

Disc swelling and mild initial visual acuity loss predict a better short-term visual acuity outcome in bilateral acute optic neuritis

Bilateral acute optic neuritis (AON) is rare in adults in Western countries, but is relatively common in Asian populations. We aimed to document clinical features in Chinese patients with bilateral AON, and to identify factors that are predictive of visual acuity outcome. We reviewed 41 patients (23 males, 18 females; age 18-74 years) diagnosed with bilateral AON from three centers between 2003 and 2009. Demographic and clinical data were compared to a group of patients with unilateral AON. Univariate analysis and multivariate linear regression were used to identify prognostic factors. We found that the median visual acuity (expressed as the logarithm of the minimal angle of resolution [LogMAR] scores) in our patients was 1.55 at presentation and 0.72 at discharge (p<0.001). There was a higher proportion of males (56% compared to 34%, p=0.015), a higher percentage with disc swelling (71% compared to 48%, p=0.014), and poorer visual acuity at presentation (median LogMAR scores: 1.55 compared to 1.70, p=0.001) in patients with bilateral AON than in those with unilateral AON. Both disc swelling (p=0.036) and visual acuity at presentation (p=0.023) were significantly associated with visual acuity at discharge. Our study suggests that bilateral AON has some clinical differences to unilateral AON, and that disc swelling and initial visual acuity may predict a short-term visual acuity outcome in bilateral AON.

Transepithelial photorefractive keratectomy mode using SCHWIND-ESIRIS excimer laser: initial clinical results.

AIM To evaluate postoperative pain, uncorrected visual acuity (UCVA), and cornea haze value after transepithelial photorefractive keratectomy (T-PRK) performed with aspherical ablation profile using SCHWIND ESIRIS excimer laser. METHODS Retrospective case series. Fifty-nice eyes (32 patients) with myopia associated with or without astigmatism underwent phototherapeutic keratectomy (PTK) followed by photorefractive keratectomy (PRK) which performed by Optimized Refractive Keratecomy (ORK)-CAM software based on aspherical ablation profile using SCHWIND ESIRIS excimer laser. Postoperative pain scale was measured on a questionnaire through five levels. Haze was graded by five grades, and UCVA, manifest refraction spherical equivalent (MRSE) were analyzed. RESULTS Mean pain level was (1.37±0.613) (range: 1 to 3), the mean time picking out the soft contact lens was (6.22±1.73) days, at 3 months, UCVA was 1.0 for 40 eyes (67.8%), 0.5 for all eyes (100.0%). The UCVA was significantly less than the preoperative best spectacle corrected visual acuity (BSCVA) (t=-2.84, P=0.006), haze value was (0.27±0.25), no patients had a haze grade up to 2. Mean MRSE was (0.76±0.96) diopter(D) by 3 months. CONCLUSION The outcomes from this study show that using the SCHWIND ESIRIS aspherical ablation profile for transepithelial PRK has a good visual result. The primary advantage is related to a spherical ablation profile, automatically considers the ablation volume of the stroma and the accurate and smooth removal of the epithelium with PTK. Additional studies are needed to determine long-term outcomes.

Vision-Related Quality of Life Tends to be More Severely Impaired in Patients with Dysthyroid Optic Neuropathy

Abstract Purpose: Dysthyroid optic neuropathy (DON) is the most severe condition in thyroid eye disease (TED); however, no study has been conducted to assess quality of life in these patients to date. The aim of this study was to evaluate vision-related quality of life in TED patients with DON using a Chinese version of the 25-item National Eye Institute Visual Function Questionnaire (CHI-VFQ-25). Methods: The CHI-VFQ-25 scores were compared for 23 TED patients with DON and 13 TED patients without DON. The correlations between the clinical characteristics and subscale scores on the CHI-VFQ-25 and the floor and ceiling effects of the CHI-VFQ-25 were also assessed. Results: Patients with DON scored significantly lower than patients without DON on the CHI-VFQ-25 (composite score: 54 versus 77, respectively, p = 0.001). Many subscales were significantly correlated with the severity and activity of the disease (p < 0.05). In patients with DON, no floor effects were found, and ceiling effects were only observed for Color vision, Peripheral vision and Social function. Role limitations and Mental health were the lowest scores in all the subscales. Conclusions: The current study showed that vision-related quality of life tended to be more severely impaired in TED patients with DON than in patients without DON. The CHI-VFQ-25 may be a promising tool to estimate the benefits of interventions in patients with DON.

8-iso-prostaglandin-F2α: a possible trigger or accelerator of diabetic retinopathy

Diabetes mellitus (DM) is a global disease, the number of patients of which is predicted to rise to about 380 million by 2025 by the World Health Organization (WHO)[1]. Diabetic retinopathy (DR) is one of the most sigificant complications in DM[1], and the first cause of irreversible blindness of adults in the world[2]. It occurs in 90% of patients after 20-30y from the diagnosis of DM[1], and about 5 million individuals have DR, which is responsible for approximately 5% of blindness worldwide[3]. There are two main stages of DR: proliferative DR (PDR) and non-PDR (NPDR) [2]. The hallmark of the presence of PDR is neovascularization, while no neovascularization means NPDR[4]. About 60% of diabetic patients suffer from PDR, which is the advanced form of DR[1]. Oxidative stress is defined as the increased generation of free radicals and impaired antioxidant defense which induces imbalance[5]. Because it activates other pathway (e.g. polyol pathway flux, and activation of diacylglyceol-protein kinase C pathway, etc.) and leads to other structural and functional changes, it plays a leading role in the progression of DM and its complications[6]. Oxidative stress can be measured by many indicative parameters, such as lipoperoxidation, protein oxidation, and changes in antioxidant defence system status[7]. Lipid peroxidation biomarkers included malondialdehyde, lipoperoxides and lipid hydroperoxides[7]. However, 8-iso-prostaglandin-F2α (8-iso-PGF2α), as one of the stable products of non-cyclooxygenase peroxidation of arachidonic acid, has proved to be the most available and reliable marker of lipid peroxidation in vivo[8]–[9], and it appears more sensitive and specific than other markers of oxidative stress[8]. Furthermore, 8-iso-PGF2α induces vasoconstriction, mitogenesis and persistent platelet activation[9]–[10], which can contribute to the progression of diabetes and/or its complications. Some previous studies showed that the concentration of 8-iso-PGF2α is associated with the level of acute and chronic glucose fluctuation[11]–[12], the level of hemoglobin A1c (HbA1c), and fasting glucose[13], which might lead to the onset and/or progression of DR. To the best of our knowledge, however, there has been no studies about the relationship between the level of plasma 8-iso-PGF2α and the onset and/or progression of DR so far.

Keeping an Eye on Optic Neuritis Studies in Mainland China

We read with great interest the review article by Dr. Woung and associates.1 They reviewed the recent important studies on optic neuritis in Asia, and compared them with those in Western countries. Their article included the studies addressed in Taiwan, Japan, India, and Singapore. However, several important studies in mainland China had not been included. We would like to review them in this letter. Almost all the studies in Asia that were published in the English language investigated unilateral and bilateral acute optic neuritis (AON) simultaneously. In the Optic Neuritis Treatment Trial (ONTT), however, the investigators only recruited the patients with unilateral AON.2 According to the literature, the proportion of bilateral AON in Asia is 25–33%.3 It is unsuitable to mix bilateral and unilateral AON, and to compare them with ONTT due to the significantly different features of bilateral and unilateral AON. In mainland China, Dr. Du described unilateral and bilateral AON separately,3,4 and found that bilateral AON has some clinical differences from unilateral AON, including a higher prevalence of male cases and disc swelling, and more severe initial visual loss, but quicker visual recovery.3 In our experiences, considerable Chinese patients with AON have a very poor visual prognosis.4,5 Dr. Lai and associates studied this subgroup of Chinese patients, and found that these patients have a high positive rate of anti-aquaporin-4 antibody (neuromyelitis optica immunoglobulin G),6,7 which is a highly sensitive and specific antibody in patients with neuromyelitis optica. For this reason, Dr. Lai’s studies had partly demonstrated the hypotheses proposed by Dr. Du, that a proportion of Chinese patients with AON might develop neuromyelitis optica during long-term follow-up, or might be a forme fruste of neuromyelitis optica.8 Although most knowledge of clinical aspects of optic neuritis is from the Optic Neuritis Treatment Trial, some cases in the Optic Neuritis Treatment Trial also had poor visual recovery, and the reason remains unclear, which is similar to the situation clinicians in China have to face almost every day. We hope our colleagues in the world keep an eye on optic neuritis studies in mainland China.

Misdiagnosis of Peripapillary Staphyloma as Retrobulbar Tumour: A Case Report

We describe a 10-year-old Chinese girl with blurred vision in her left eye over a month and an optic nerve “mass” of her left orbit shown on computed tomography. The patient was initially misdiagnosed as having a retrobulbar tumour. However, detailed fundus examination showed a very deep excavation surrounding the disc and magnetic resonance imaging revealed excavation of the posterior wall connected to the vitreous cavity. These findings suggested a diagnosis of peripapillary staphyloma. The reasons for the misdiagnosis are discussed.