Analysis of Phenotypes Associated with Deficiency of PAX6 Haplotypes in Chinese Aniridia Families.

OBJECTIVE: To examine the clinical phenotype and genetic deficiencies present in Chinese aniridia families with PAX6 haplotype deficiency. METHODS: A comprehensive questionnaire and ophthalmological assessments were administered to both affected patients and unaffected relatives. The clinical feature analysis included the evaluation of visual acuity, intraocular pressure, slit-lamp anterior segment examination, fundus photography, and spectral domain optical coherence tomography. To identify the mutation responsible for aniridia, targeted next-generation sequencing was used as a beneficial technique. RESULTS: A total of 4 mutations were identified, consisting of two novel frameshift mutations (c.314delA, p.K105Sfs*33 and c.838_845dup AACACACC, p.S283Tfs*85), along with two recurring nonsense mutations (c.307C>T, p.R103X and c.619A>T, p.K207*). Complete iris absence, macular foveal hypoplasia, and nystagmus were consistent in these PAX6 haplotype-deficient Chinese aniridia families, while corneal lesions, cataracts, and glaucoma exhibited heterogeneity both among the families and within the same family. CONCLUSION: In our study, two novel PAX6 mutations associated with aniridia were identified in Chinese families, which expanded the phenotypic and genotypic spectrum of PAX6 mutations. We also analyzed the clinical characteristics of PAX6 haplotype deficiency in Chinese aniridia families.

Cone Density Distribution and Related Factors in Patients Receiving Hydroxychloroquine Treatment.

Purpose: Hydroxychloroquine is an effective treatment for rheumatic diseases; however, retinal damage is a possible side effect. We aimed to identify the retinal area and related risk factors associated with cone density reduction caused by hydroxychloroquine. Methods: We recorded the retinal images of patients with rheumatic diseases taking hydroxychloroquine (n = 44) and compared them with images of healthy controls (n = 107). Cone density was obtained in vertical and horizontal axes. Regions of decreased cone density and associations between age, rheumatic disease type, dosage for ideal body weight, and cone density were evaluated. Results: Cone densities were significantly lower in hydroxychloroquine-treated patients than in sex- and age-matched controls in the vertical axis (P < 0.001), with no significant difference in the horizontal axis (P = 0.120); in healthy elderly than in healthy young people in the horizontal axis (P < 0.001), with no significant difference in the vertical axis (P = 0.100); in hydroxychloroquine-treated elderly than in hydroxychloroquine-treated young patients in both axes (both P < 0.05); among patients with different rheumatic disease types, with no significant difference in the vertical axis (P = 0.294). The daily dose was negatively correlated with cone density in the vertical axis and inferior quadrant. Conclusions: Hydroxychloroquine reduces retinal cone cell density in the vertical axis. Cone density loss in the horizontal axis increases with age; further, hydroxychloroquine dosage is negatively correlated with cone density in the vertical axis and inferior quadrant. Early screening of hydroxychloroquine-related retinal injury should consider changes in cone density in the vertical axis.

Traumatic dislocation of the iris into the vitreous cavity with intact lens: a case report.

BACKGROUND: Traumatic aniridia occurs when the iris is extruded from the eye and is often accompanied by lens injuries. However, traumatic aniridia due to dislocation of the iris into the vitreous cavity without lens damage has never been reported. CASE PRESENTATION: A 30-year-old man presented with visual loss and pain for 6 h after a thin wire injured his right eyeball. Ophthalmologic examinations manifested a 2 mm full-thickness corneal laceration and total hyphema. An intact clear lens, healthy attached retina, and almost complete iris tissue in the vitreous cavity were found after resolution of hyphema the next day. Further examination revealed that the defect in the zonule below the corneal wound was the path for the iris to enter the vitreous cavity. The patient opted for nonsurgical treatment until pigment granules and opacity were observed in the vitreous cavity after 50 days. Vitrectomy was performed to remove the dislocated iris. CONCLUSIONS: The presentation of this unique case indicates that the torn iris was displaced to the vitreous cavity with an intact lens and missing local zonula instead of out the corneal laceration after a penetrating injury. The type of injury, mechanism, and force on the spot may contribute to the occurrence of this rare condition. Instead of artificial irises, tinted glasses were more appropriate treatment option for this patient. Peripheral retinal examination was essential in the management of this case. In such cases, the iris in the vitreous cavity should be resected to prevent complications.

Various phenotypes of autosomal dominant cone-rod dystrophy with cone-rod homeobox mutation in two Chinese families.

AIM: To present the clinical manifestations of 5 autosomal dominant cone-rod dystrophy (adCORD) patients from two Chinese families with cone-rod homeobox (CRX) mutation (p.R41W), and to explore the clinical heterogeneity of adCORD with CRX mutation (p.R41W). METHODS: Interrogation and ophthalmological examinations were undertaken in all patients and unaffected members. Analysis of clinical features was performed by visual acuity, slit lamp examination, visual field examination, fundoscopy, autofluorescence and spectral domain optical coherence tomography. Targeted next-generation sequencing was applied as a useful tool to identify the causative mutation of CORD genes. RESULTS: A CRX missense mutation c.121C>T was identified in all patients, resulting in an amino acid change from arginine acid to tryptophan (p.R41W). The patients presented with early onset, progressive and different severities with CORD. CONCLUSION: This is the first report of the clinical phenotype of CRX mutation (p.R41W) in Chinese families, and the mutation can lead to a wide range of various retinal phenotypes.

WFS1-Associated Optic Neuropathy: Genotype-Phenotype Correlations and Disease Progression.

OBJECTIVE: To evaluate the pattern of vision loss and genotype-phenotype correlations in WFS1-associated optic neuropathy (WON). DESIGN: Multicenter cohort study. METHODS: The study involved 37 patients with WON carrying pathogenic or candidate pathogenic WFS1 variants. Genetic and clinical data were retrieved from the medical records. Thirteen patients underwent additional comprehensive ophthalmologic assessment. Deep phenotyping involved visual electrophysiology and advanced psychophysical testing with a complementary metabolomic study. MAIN OUTCOME MEASURES: WFS1 variants, functional and structural optic nerve and retinal parameters, and metabolomic profile. RESULTS: Twenty-two recessive and 5 dominant WFS1 variants were identified. Four variants were novel. All WFS1 variants caused loss of macular retinal ganglion cells (RGCs) as assessed by optical coherence tomography (OCT) and visual electrophysiology. Advanced psychophysical testing indicated involvement of the major RGC subpopulations. Modeling of vision loss showed an accelerated rate of deterioration with increasing age. Dominant WFS1 variants were associated with abnormal reflectivity of the outer plexiform layer (OPL) on OCT imaging. The dominant variants tended to cause less severe vision loss compared with recessive WFS1 variants, which resulted in more variable phenotypes ranging from isolated WON to severe multisystem disease depending on the WFS1 alleles. The metabolomic profile included markers seen in other neurodegenerative diseases and type 1 diabetes mellitus. CONCLUSIONS: WFS1 variants result in heterogenous phenotypes influenced by the mode of inheritance and the disease-causing alleles. Biallelic WFS1 variants cause more variable, but generally more severe, vision and RGC loss compared with heterozygous variants. Abnormal cleftlike lamination of the OPL is a distinctive OCT feature that strongly points toward dominant WON.

Novel mutations in the BEST1 gene cause distinct retinopathies in two Chinese families.

AIM: To describe the clinical heterogeneity of patients with novel mutations in BEST1. METHODS: All the members in the two Chinese families underwent detailed clinical evaluations including best-corrected visual acuity, slit-lamp examination, applanation tonometry, and dilated fundus examination. Fundus autofluorescence, fundus fluorescein angiography, spectral-domain optical coherence tomography, electrooculography, and electroretinogram were also performed. Genomic DNA was extracted from venous blood for all the participants. The targeted next-generation sequencing of inherited retinal disease-associated genes was conducted to identify the causative mutation. RESULTS: A novel BEST1 missense mutation c.41T>C (p.Leu14Ser) was identified in Family 1. It was co-segregated with the phenotype of best vitelliform macular dystrophy (BVMD) and bioinformatics analysis confirmed it was harmful. Another novel BEST1 frameshift mutation c.345_346insGGCAAGGACG (p.Glu119Glyfs*116) and a novel USH2A missense mutation c.12560G>A, p.Arg4187His were identified in family 2 with retinitis pigmentosa (RP), which might interact and lead to the phenotype of RP. CONCLUSION: Two novel mutations in the BEST1 gene in two unrelated families with distinct phenotypes and BEST1 mutation accompanied with USH2A mutation would result in RP, which could be enormously helpful in understanding the pathogenesis of the inherited retinal disease caused by a BEST1 mutation.

The Evaluation of the Maculopathy Using Dynamic Contrast-enhanced MRI in Patients with Proliferative Diabetic Retinopathy.

BACKGROUND: Dynamic Contrast-enhanced Magnetic Resonance Imaging (DCE-MRI) technique could not only quantify blood-retinal barrier (BRB) breakdown leading to macular edema associated with diabetes, but also provide a two-dimensional imaging method that is not interfered by refracting media. OBJECTIVE: The current study was aimed to evaluate the macular change in the patients with diabetic retinopathy using DCE-MRI technique. METHODS: Twenty patients with Diabetic Retinopathy (DR) and 20 Normal Controls (NC) were included. The fast spoiled gradient echo sequence was used to perform dynamic contrast T1WI enhancement on 3.0T MR system. The macular region, optic papila and nasal retina were performed with quantitative DCE-MRI evaluation using Omni-Kinetics software. RESULTS: The maximal concentration, the area under the concentration-time curve (AUCconcentration-time) and maximal slope of macular region were significantly higher in DR [0.270(0.03,1.20)mmol/ 100ml, 2.71(0.04,9.91) mmol*min and 0.38(0.06,3.18) mmol/min, respectively] than that [0.169(0.03,0.72) mmol/1.25(0.13,10.41) mmol*min and 0.245(0.06,1.34) mmol/min] in NC (U value = 515.00 and P value = 0.080, U value = 433.00 and P value = 0.000, and U value = 563.00 and P value = 0.023, respectively). The receiver operating characteristic curve (ROC) analysis demonstrated that the area under AUCconcentration-time was 0.729±0.058 with the cut-off value 1.479 mmol*min (sensitivity 80.00% and specificity 62.50%) for macular region. CONCLUSION: The quantitative DCE-MRI technique could be used to evaluate the maculopathy associated with diabetic retinopathy.

A novel mutation of FOXC1 in a Chinese family with Axenfeld-Rieger syndrome.

Axenfeld-Rieger syndrome (ARS) is a disorder affecting the anterior segment of the eye and causing systemic malformations, and follows an autosomal-dominant inheritance pattern. The aim of the present study was to identify the underlying cause of ARS in a Chinese family. Genomic DNA was extracted from the peripheral blood of the subjects from a family with ARS. The pathogenic variant was identified by targeted next-generation sequencing and confirmed by Sanger sequencing. A novel heterozygous mutation of the forkhead box (FOX)C1 gene (c.1494delG, p.G499Afs*20) was detected in all affected members of the family, while no mutation was identified in the unaffected members or in the 150 normal controls. The affected members exhibited typical ocular and craniofacial anomalies. The results of the present study demonstrated that a novel deletion in exon 1 of the FOXC1 gene caused ARS in this Chinese family.

A new perspective for analyzing clinical characteristics of idiopathic retinal vasculitis, aneurysms, and neuroretinitis syndrome.

PURPOSE: We aimed to analyze the clinical characteristics of idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome. Furthermore, we aimed to correlate the number and location of retinal aneurysms with the size of retinal non-perfusion area and neovascularization. METHODS: Six patients with IRVAN syndrome (1 male and 5 females, age 5-38 years) were enrolled in this study. Fundus fluorescein angiography (FFA) was used to determine the total number of retinal aneurysms, number of aneurysms within the first branch of the retinal artery, minimum distance between the non-perfusion margin and the optic disc, and the number of retinal aneurysms in each quadrant, as well as the type of neovascularization. RESULTS: The size of the non-perfusion area was positively correlated with the total number of retinal aneurysms, the number of aneurysms within the first branch of the retinal artery, and the number of retinal aneurysms in each quadrant (P < 0.05). During the 5-year follow-up, one patient exhibited a dynamic change in the number and location of retinal aneurysms. CONCLUSIONS: In IRVAN syndrome, the number and location of retinal aneurysms correlate with the size of retinal non-perfusion area and type of neovascularization.

Recombination and identification of human alpha B-crystallin.

AIM: To recombine the human alpha B-crystallin (αB-crystallin) using gene cloning technology and prokaryotic expression vector and confirm the biological activity of recombinant human αB-crystallin. METHODS: Cloning the human αB-crystallin cDNA according to the nucleotide sequence of the human αB-crystallin, constructing the pET-28/CRYAB prokaryotic expression plasmid by restriction enzyme digestion method, and stably expressing transformed into the Escherichia coli (E. coli) DH5 alpha. The recombinant human αB-crystallin was purified by Q sepharose. By enzyme digestion analysis, Western blotting and sequencing, the recombinant human αB-crystallin was identified and the activity of its molecular protein was detected. RESULTS: Compared with the gene bank (GeneBank), the cloned human sequence of human αB-crystallin cDNA has the same open reading frame. Identification and sequencing of the cloned human αB-crystallin cDNA in prokaryotic expression vector confirmed the full length sequence, and the vector was constructed successfully. The E. coli containing plasmid pET-28/CRYAB induced by isopropyl-ß-D-thiogalactoside successfully expressed the human αB-crystallin. Insulin confirmed that the recombinant human αB-crystallin has a molecular chaperone activity. CONCLUSION: The prokaryotic expression vector pET-28/CRYAB of recombinant human αB-crystallin is successfully constructed, and the recombinant human αB-crystallin with molecular chaperone activity is obtained, which lay a foundation for the research and application of the recombinant human αB-crystallin and its chaperone activity.

A novel mutation in the VHL gene in a Chinese family with von Hippel-Lindau disease.

BACKGROUND: Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited cancer syndrome, and VHL is identified as a tumor suppressor gene. The main objective of this study was to identify disease-causing mutations in a Chinese family affected with VHL disease. METHODS: Genomic DNA was extracted from peripheral blood from a Chinese family with VHL. A predicted pathogenic variant was identified by targeted exome capture technology and next-generation sequencing. RESULTS: A novel heterozygous mutation (c.349 T > A, p.W117R) was detected in affected family members. No mutation was detected in unaffected family members or in the 150 normal controls. The mutation segregated with the disease phenotype throughout three generations. Histopathological examination revealed the characteristics of hemangioblastoma. CONCLUSIONS: A novel W117R was detected in the VHL gene that caused retinal hemangioblastomas in affected members of a Chinese family.

Early Diagnosis of Recurrent Optic Neuritis Using Contrast-Enhanced T2 Fluid-attenuated Inversion Recovery Imaging: a Case Report.

The diagnosis of the recurrent optic neuritis is commonly established clinically, and sometimes it could be challenging because the involved optic nerve does not always show significant enhancement on conventional contrast enhanced-T1 weighted imaging (CE-T1WI). In this paper, we reported a middle-aged female with early diagnosis of recurrent optic neuritis using contrast-enhanced T2 fluid-attenuated inversion recovery imaging (CE-T2FLAIR). The involved optic nerve presented evident enhancement on CE-T2FLAIR and no enhancement on CE-T1WI. This case suggested that the CE-T2FLAIR may be a useful diagnostic tool specifically for the recurrent optic neuritis in clinical practice.

Novel compound heterozygous mutation in the POC1B gene underlie peripheral cone dystrophy in a Chinese family.

PURPOSE: To describe the clinical characteristics of a Chinese family with peripheral cone dystrophy (PCD) and identify the gene mutations causing PCD. METHODS: The Chinese PCD pedigree underwent comprehensive ophthalmic examinations, including visual acuity, slit lamp examination, fundoscopy, visual field examination, autofluorescence, fluorescence fundus angiography and indocyanine green angiography, full-field electroretinograms, and spectral-domain optical coherence tomography. The targeted next-generation sequencing of COD or cone-rod dystrophy (CORD) genes was used to identify the causative mutation. RESULT: The fundus characteristics of the Chinese patient were consistent with PCD. The novel compound heterozygous mutation, c.1354C>T and c.710A>G, in POC1B was identified in the patient, the mutations were segregated with the PCD phenotype in the family and were absent from ethnically matched control chromosomes. Prediction analysis demonstrated the novel missense mutation, POC1B c.710A>G, might be damaging. CONCLUSIONS: PCD was a type of COD or CORD and the novel compound heterozygous mutation in POC1B was responsible for PCD phenotype in the family.

Calibration and standardisation of graded optic nerve injuries in rats.

OBJECTIVES: To calibrate and standardise an animal model of graded optic nerve injury (ONI) in rats to facilitate future inter-laboratory data comparisons, focussing on quantification of injury intensity, injury severity, and the correlation between them. METHODS: A pair of cross-action forceps or a pair of artery clips was used to induce optic nerve (ON) crush injuries. A lever principle and a simplified method were used to measure the crushing force. The simplified method directly measured weights as an external force exerted on the tip of the forceps or clips, which was just sufficient to maintain a gap and was equivalent to the closing (crush) force. The impulse and averaged impulse were explored as physical quantities to compare injury intensities. Graded ONIs were made by crushing the ON for 3, 6, 12, 30 or 60 seconds by the cross-action forceps, or 5, 10 or 15 seconds by the artery clips. The injury severity was evaluated by counting surviving retinal ganglion cell (RGC) through applied FluoroGold to the superior colliculus and lateral geniculate body before ON crush, intact RGC counting by applied FluoroGold after ON crush, and ON axon counting. RESULTS: Similar results were obtained by the lever principle method and the simplified method. The crushing force of the cross-action forceps and the artery clips was 148.0 gram force (gf) and 32.4 gf, respectively. The graded ONI animal models were successfully created in rats without retinal ischaemia post-trauma. The averaged impulse produced by the artery clips for 15 seconds was equal to that produced by a 3-second crush of the cross-action forceps. The correlation between injury intensity and injury severity was fitted for a power function. DISCUSSION: Our results provide a simplified and effective means to quantify and analyse data from ON crush studies compared with previously reported animal models.

Characterization of macular thickness changes in Leber's hereditary optic neuropathy by optical coherence tomography.

BACKGROUND: To characterize macular thickness (MT) changes in Leber's hereditary optic neuropathy (LHON) patients by cirrus HD-optical coherence tomography (OCT), and to study the correlation between MT and best corrected visual acuity (BCVA). METHODS: Fifty-two eyes from 52 consecutive LHON patients and 14 eyes from 14 age- and sex-matched healthy controls were scanned by OCT. Affected eyes were classified into five groups according to disease duration (1st group: ≤3 months; 2nd group: 3-6 months; 3rd group: 6-9 months; 4th group: 9-12 months; and 5th group: >12 months). MT was compared and analyzed. The correlation between BCVA and MT was calculated. RESULTS: Less than six months after LHON onset, the cube average thickness (CAT) and the MT in the superior, nasal, inferior, and temporal quadrants of the inner ring and the MT in the nasal quadrant of the outer ring were decreased (P < 0.005); at 3-6 months onset, the MT of the temporal quadrants of the outer ring was decreased (P = 0.045); after 6 months, the MT was significantly thinner in all measurements (P < 0.01) except for the central ring. The BCVA was significantly different between each group and controls (P < 0.05), but there was no significant correlation among the five groups (P = 0.666). There was no significant correlation between the BCVA and CAT (P = 0.893). CONCLUSIONS: The MT thinned before the retinal nerve fiber layer and this occurred with a particular sequence. Our results provide potential diagnostic information for LHON.

Pigmented paravenous retinochoroidal atrophy (Review).

Pigmented paravenous retinochoroidal atrophy (PPRCA) is an uncommon disease characterized by perivenous aggregations of pigment clumps associated with peripapillary and radial zones of retinochoroidal atrophy that are distributed along the retinal veins. Patients are usually asymptomatic and the disease process is non-progressive or slow and subtly progressive. It is commonly bilateral and symmetric. The cause of the condition may be unknown or idiopathic, although a dysgenetic, degenerative, hereditary etiology or even an inflammatory cause has been hypothesized. A non-inflammatory cause is referred to as primary, while inflammation-associated PPRCA is referred to as secondary or pseudo PPRCA. The present study reviewed and summarized the features of PPRCA.

Clinical characteristics of nonglaucomatous optic disc cupping.

Pathological optic disc cupping (ODC) is predominantly referred to as glaucoma; however, it is not only glaucoma that leads to pathological optic disc excavation. A number of other nonglaucomatous diseases also result in optic atrophy and excavation of the optic disc. Therefore, in the present study, the etiology of nonglaucomatous optic disc cupping (NGODC) was analyzed and differentiated from glaucomatous optic disc cupping (GODC). The morphology and clinical data of 19 eyes, from 12 patients exhibiting NGODC, were analyzed. Of the 12 cases, none were diagnosed with glaucoma, four presented with optic neuritis, one with Devic's disease, one with Leber's hereditary optic neuropathy, two with pituitary adenoma, one with basal ganglia cerebral hemorrhage, one with cilioretinal artery occlusion associated with central retinal vein occlusion, one with central retinal artery occlusion and the remaining patient exhibited optic nerve injuries. The key features that differentiated NGODC from GODC were the color of the optic disc rim and the correlation between visual field defects and the disc appearance. The focally notched disc also aided in distinguishing between the two disorders. The results of the present study indicated that it is critical to acknowledge that nonglaucomatous diseases also lead to ODC and that distinguishing between them is necessary.

Characterization of retinal nerve fiber layer thickness changes associated with Leber's hereditary optic neuropathy by optical coherence tomography.

In the present study, the changes in the retinal nerve fiber layer (RNFL) thickness associated with Leber's hereditary optic neuropathy (LHON) were examined by Cirrus high definition-optical coherence tomography (OCT), and the correlation between the RNFL thickness and the best corrected visual acuity (BCVA) was evaluated. A cross-sectional study was performed. Sixty-eight eyes from patients with LHON and 30 eyes from healthy individuals were scanned. Affected eyes were divided into 5 groups according to disease duration: Group 1, ≤3 months; group 2, 4-6 months; group 3, 7-9 months; group 4, 10-12 months; and group 5, >12 months. The RNFL thickness of the temporal, superior, nasal and inferior quadrants and the 360° average were compared between the LHON groups and the control group. The eyes in groups 1 and 2 were observed to have a thicker RNFL in the superior, nasal and inferior quadrants and a higher 360°-average RNFL thickness compared with those of the control group (P<0.05), the RNFL was observed to be thinner in the temporal quadrant in groups 1 and 2. The eyes in groups 3 and 4 showed a thinner RNFL in the temporal (P=0.001), superior and inferior (both P<0.05) quadrants, and a lower 360°-average RNFL thickness as compared with controls (P=0.001). No significant correlation was identified between BCVA and RNFL thickness. RNFL thickness was observed to undergo a unique process from thickening to thinning in the patients with LHON. Changes in different quadrants occurred at different time periods and the BCVA was not found to be correlated with RNFL thickness.

Clinical features and differential diagnosis of acute idiopathic blind spot enlargement syndrome.

PURPOSE: To study the clinical manifestations and the diagnostic and differential diagnostic characteristics of acute idiopathic blind spot enlargement syndrome (AIBSES). METHODS: Six patients diagnosed with AIBSES underwent complete eye examinations including fundus photography, fundus fluorescein angiography(FFA), indocyanine green angiography (ICGA), optical coherence tomography (OCT), electroretinogram (ERG), and visual field examinations. RESULTS: All patients had enlarged blind spots of variable sizes and densities. Three eyes had mild swelling of the optic disc and one eye had peripapillary scarring that corresponded to the permanent field defect. Two patients who underwent FFA had fluorescein leakage of blood vessels around the optic disc and ICGA highlighted diffuse, small hypofluorescent spots scattering throughout the posterior pole. OCT showed that the inner and outer segment (IS/OS) line were absent in five patients and the middle cone outer segment tip line was absent in the nasal macular area in one eye. CONCLUSION: AIBSES is a rare outer retinopathy. Visual field examination and OCT are the most important means of detection. ICGA and FAF can determine the range of lesions earlier, and the progress of the disease should be taken into account when making a diagnosis.

Evaluation of tear malate dehydrogenase 2 in mild dry eye disease.

PURPOSE: To evaluate the effect of tear malate dehydrogenase 2 on monitoring ocular surface injury in mild dry eye (DE) disease. METHODS: A total of 15 DE patients (30 eyes) with mild subjective symptoms but no ocular surface fluorescein staining signs were enrolled in this study (DE group). The control group was 15 healthy age- and sex-matched volunteers (30 eyes). All subjects were asked to fill out a DE symptoms questionnaire and take different tests including tear MDH and MDH2 activities evaluation, tear breakup time (TBUT), Schirmer I, and slit-lamp examination of the ocular surface. We investigated different changes in tear MDH and MDH2 activities in the DE group and control group, discussed the association between tear MDH2 activity and DE symptoms, and the relationship between tear MDH2 activity and diagnostic tests (Schirmer I and TBUT). We also analyzed the changes in tear MDH2 activities after the treatment with artificial tears. RESULTS: Tear MDH activities in the DE group and control group were 288 ± 102 U/L and 259 ± 112 U/L, respectively, and this difference was not statistically significant (P > 0.05). The tear MDH2 activities in DE group were significantly increased compared with control group. Tear MDH2 was significantly and negatively correlated with the Schirmer's value (r = -0.733, P < 0.01) and the TBUT value (r = -0.841, P < 0.01). MDH2 also had a significant positive correlation with soreness symptoms (r = 0.687, P < 0.01). Treatment with artificial tears relieved or eliminated all discomfort symptoms, together with a considerable decrease in MDH2 activities (P < 0.01), but no significant changes in the Schirmer and the TBUT tests were observed. CONCLUSION: Tear MDH2 activity can indicate ocular surface injury in mild DE patients and may be used to monitor the response to therapy.