Pulsed Oral Azithromycin vs 6-Week Oral Doxycycline for Moderate to Severe Meibomian Gland Dysfunction: A Randomized Clinical Trial.

Importance: The treatment of moderate to severe meibomian gland dysfunction (MGD) with oral doxycycline requires a 6-week course of treatment and has frequent adverse effects (AEs), which may be associated with poor compliance. Objective: To determine if the AEs of a 3-week course of oral azithromycin were equivalent to the AEs of a 6-week course of oral doxycycline. Design, Setting, and Participants: This double-masked randomized clinical trial was conducted at a referral center in Thailand from September 2018 to May 2022. Participants with moderate to severe MGD judged unresponsive to conservative management were included. Interventions: Patients were randomized 1:1 to receive oral azithromycin (1 g once per week for 3 weeks) or oral doxycycline (200 mg daily for 6 weeks). Main Outcomes and Measures: After initiating therapy, the study team assessed the total MGD score and Ocular Surface Disease Index (OSDI) score at the initial visit, at 6 weeks, and at 8 weeks, and assessed AEs at 6 weeks and 8 weeks. The prespecified equivalence margins for MGD score and OSDI score were set at ±2 and ±9, respectively. Results: A total of 137 eyes from 137 patients were randomized into groups, 68 eyes in the azithromycin group and 69 eyes in the doxycycline group (female, 66.4%; mean age, 62.0 [SD, 15.1] years). The adjusted mean difference of total MGD scores between groups at week 6 and week 8 were -0.33 (95% CI, -1.70 to 1.03; P for equivalence = .01) and 0.13 (95% CI, -1.59 to 1.84; P for equivalence = .02), respectively. The adjusted mean difference of OSDI between groups score at week 6 and week 8 was -1.20 (95% CI, -5.31 to 2.91; P for equivalence < .001) and -1.59 (95% CI, -5.73 to 2.55; P for equivalence < .001), respectively. In addition, patients treated with azithromycin had fewer gastrointestinal AEs (4.4% vs 15.9%; risk difference, 11.5%; 95% CI 1.6%-21.4%; P = .03). Conclusions and Relevance: These data support an equivalency of effects of azithromycin as compared with doxycycline for MGD score and OSDI score at both follow-up times. The study did not show more gastrointestinal AEs in the azithromycin group. The reduced dosing and potentially fewer gastrointestinal AEs associated with azithromycin support its use as an alternative to doxycycline for at least 6 weeks. Trial Registration: ThaiClinicalTrials.org Identifier: TCTR20180810001.

Prevalence of symptomatic dry eye disease with associated risk factors among medical students at Chiang Mai University due to increased screen time and stress during COVID-19 pandemic.

Dry eye disease (DED) is one of the most common ophthalmological disorders, resulting from several systemic and ocular etiologies including meibomian gland dysfunction (MGD). During the COVID-19 pandemic, medical students are among the high-risk group for DED, mainly due to the increasing use of a visual display terminal (VDT) for online lectures and psychological stress from encountering several changes. Our study aimed to explore the prevalence of DED using the symptom-based definition and potential risk factors in medical students. This is a prospective cross-sectional study that included medical students at Chiang Mai University between November 2020 and January 2021. All participants were assessed using the Ocular Surface Disease Index (OSDI) questionnaire, the Thai version of the 10-Item Perceived Stress Scale-10 (T-PSS-10), the LipiView® II interferometer, and an interview for other possible risk factors. Overall, 528 participants were included in the study; half of the participants were female. The prevalence of DED was 70.8%. In the univariate analysis, female sex, contact lens wear, and T-PSS-10 stress scores were significantly higher in the DED group (P = 0.002, 0.002, and <0.001, respectively). Moreover, participants with severe DED were likely to have higher meibomian gland tortuosity but not statistically significant. In the multivariate analysis, contact lens use and T-PSS-10 score were significant risk factors associated with the severity of DED. In conclusions, the prevalence of DED in medical students was as high as 70.8%. Contact lens use and psychological stress evaluated using the T-PSS-10 questionnaire had a significant correlation with a risk of DED. Female gender and duration of VDT use were also associated. Most of the risk factors were modifiable and may be used as initial management in patients with DED.

Two-Step Transepithelial Photorefractive Keratectomy with WaveLight EX500 Platform for Adolescents and Adults with Low to Moderate Myopia: A 12-Month Comparative Evaluation.

PURPOSE: To compare the visual and refractive results obtained after two-step TransPRK using an EX500 excimer laser for low to moderate myopic correction in adolescents and adults. PATIENTS AND METHODS: Retrospectively, 91 eyes of 52 patients were categorized into four groups based on age and level of myopia. The demographics, data of efficacy, safety, predictability, stability, and post-operative complications were evaluated at 1, 3, 6, and 12 months post-operatively. RESULTS: At 1-month, adolescents with low myopia achieved the highest mean efficacy index (P =0.034). The efficacy indices continuously increased during the 1-year follow-up in all groups, except in adolescents with moderate myopia. The highest safety and efficacy indices were recorded in adolescents with low myopia at 1-year. Post-operative spherical equivalent within ±0.50 D at 1 year was 48.75% of all treated eyes; however, the final mean refractive spherical equivalent (MRSE) was under-corrected in all groups. By month 3, the percentage of eyes that had grade 0.5 haze was most prevalent in adolescents with moderate myopia (P <0.001). CONCLUSION: two-step TransPRK using an EX500 proved to be an effective, predictable, stable and safe procedure for the correction of low to moderate myopia with or without astigmatism at 1 year. Adolescents with low myopia achieved the best-post-operative UDVA, efficacy and safety indices. Adolescents tolerated night visual problems and dry eye symptoms better than adults.

Fungal Keratitis in Northern Thailand: Spectrum of Agents, Risk Factors and Putative Virulence Factors.

Fungal keratitis (FK) is a serious ocular infection that can result in various degrees of vision loss, including blindness. The aim of the study was to identify and retrospectively review all FK cases diagnosed between August 2012 and December 2020 at a tertiary care hospital in northern Thailand with a specific focus on epidemiologic features, including season, patient sex and age, the spectrum of pathogens, and presence of certain putative virulence factors. Of 1237 patients with corneal ulcers, 294 (23.8%) were confirmed by direct microscopic examination and/or fungal culture. For the positive cases, direct examinations of Calcofluor white (CW) stains and KOH mounts were found in 97.3% (286/294) and 76.5% (225/294), respectively (p < 0.05). Of the cases diagnosed by microscopy and culture, fungi were isolated in 152 (51.7%), with Fusarium spp. being the most frequently identified (n = 69, 45.5%) followed by dematiaceous fungi (n = 45, 29.6%) and Aspergillus spp. (n = 18, 11.8%). The incidence of FK was higher in the rainy season of July to October. The mean age was 54.4 ± 14.4 (SD) years, with a range of 9-88 years. Males (75.8%) were affected significantly more than females (24.2%) (p < 0.05). Of 294 patients, 132 (44.9%) were middle-aged adults (41-60 years) and 107 (36.4%) were older than 60 years. Trauma to the eye by soil or vegetative matter were the most common preceding factors (188/294; 64.0%). We assessed two virulence factors. First, 142 of the 152 culture-positive FK cases were due to molds, indicating that hyphal morphogenesis is extremely important in disease. We also demonstrated that fungal melanization occurs in the molds during the course of FK by applying a melanin-specific monoclonal antibody (MAb) that labeled fungal elements in corneal samples of patients, and melanin particles derived from the hyphae were also recovered after treatment of the samples with proteolytic enzymes, denaturant and hot concentrated acid. In summary, we demonstrate that northern Thailand has a high rate of FK that is influenced by season and males engaged in outside activities are at highest risk for disease. Moulds are significantly more commonly responsible for FK, in part due to their capacity to form hyphae and melanins. Future studies will examine models of fungal corneal interactions and assess additional factors of virulence, such as secreted enzymes, to more deeply decipher the pathogenesis of FK.

The Clinical Features and Prognostic Factors for Treatment Outcomes of Dematiaceous Fungal Keratitis over 9 Years at a Tertiary Eye Care in Northern Thailand.

Dematiaceous fungal keratitis is an important etiology of visual loss, particularly in an agricultural society. From a retrospective review of medical records from 2012 to 2020, 50 keratitis cases of cultured-positive for dematiaceous fungi were presented at a tertiary care hospital in Northern Thailand. The study aimed to identify the isolated causative dematiaceous species using the PCR technique and to explore their related clinical features, including treatment prognoses. Sequencing of the amplified D1/D2 domains and/or ITS region were applied and sequenced. Of the 50 dematiaceous fungal keratitis cases, 41 patients were males (82%). In most cases, the onset happened during the monsoon season (June to September) (48%). The majority of the patients (72%) had a history of ocular trauma from an organic foreign body. The most common species identified were Lasiodiplodia spp. (19.35%), followed by Cladosporium spp. and Curvularia spp. (12.90% each). About half of the patients (52%) were in the medical failure group where surgical intervention was required. In summary, ocular trauma from an organic foreign body was the major risk factor of dematiaceous fungal keratitis in Northern Thailand. The brown pigmentation could be observed in only 26%. Significant prognostic factors for medical failure were visual acuity at presentation, area of infiltrate, depth of the lesions, and hypopyon.

Fungal keratitis at a tertiary eye care in Northern Thailand: Etiology and prognostic factors for treatment outcomes.

PURPOSE: To evaluate etiology and prognostic factors for treatment outcomes of fungal keratitis (FK). METHODS: Culture-positive FK patients between 2012 and 2017 were reviewed. Treatment outcomes were categorized into success (resolved within two weeks), slow response and medication failure (no improvement or required surgery). Etiology and risk factors for poor treatment outcomes were analyzed. RESULTS: A total of 113 eyes of 113 patients (77% males) were recruited. Ocular trauma (69.0%) was the most common predisposing factor. Of this, 80% were exposed to organic foreign bodies. The most common pathogen was Fusarium spp. (45.2%), while dematiaceous fungi were discovered in 29.6%. Medical treatment was successful in 24.8% of eyes, while 29.2% had a slow response and 42.5% failed medication. Therapeutic keratoplasty was performed in 22.1% of eyes and 11.5% eventually required eye removal. Significant risk factors for medication failure were advanced age (P = 0.005), delayed antifungal treatment (P = 0.038) and large-size lesion (P = 0.003). CONCLUSIONS: Ocular trauma was the major predisposing factor of FK in the Northern Thailand. Fusarium was the most common identified pathogen. Many cases were refractory to medications and required surgical intervention. Aging, delayed treatment and a large lesion were predictors for poor outcomes.

Twelve-Month Outcomes of the Wavefront-Optimized Photorefractive Keratectomy for High Myopic Correction Compared with Low-to-Moderate Myopia.

PURPOSE: To evaluate the 12-months outcomes of photorefractive keratectomy (PRK) in patients with high myopia (≥ 6.0 diopters, D) compared with low-to-moderate myopia (< 6.0 D). PATIENTS AND METHODS: Records of 46 patients (69 eyes) who underwent PRK for myopic and astigmatic correction between October 2015 and December 2018 were reviewed. High myopic eyes (29 eyes) were compared with low-to-moderate myopic eyes (40 eyes). All surgeries were adjunct with 0.02% mitomycin C intraoperatively. Measured outcomes included postoperative uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest refraction spherical equivalent, corneal haze rate, and any complications. RESULTS: At 12 months post-PRK, 26 eyes (89.7%) in the high myopia and 39 eyes (97.5%) in the low-to-moderate myopia group had UDVA ≥ 20/20, (p=0.30). Average postoperative logMAR UDVA at 12 months was -0.04 (20/18) and -0.11 (20/15) for the high myopia and low-to-moderate myopia groups, respectively. No eyes in either group had residual refractive errors >1 D. No eyes in both groups developed significant corneal haze at month 12. No eyes had a loss of greater than two Snellen lines of CDVA at 12 months post-surgery. The efficacy and safety indices at 12 months post-surgery were not significantly different between groups (1.06±0.26 vs.1.14±0.27, p =0.25 and 1.14±0.27 vs 1.17±0.26, p=0.60 for low-to-moderate myopia vs high myopia groups, respectively). CONCLUSION: PRK with high myopic correction provides excellent refractive outcomes and is safe, compared to those of low-to-moderate myopic correction.

Incidence and predisposing factors of anterior chamber gas bubbles during femtosecond laser flap creation.

AIM: To investigate the incidence and the predisposing factors of anterior chamber (AC) gas bubbles during femtosecond laser (FS) flap creation for laser in situ keratomileusis (LASIK). METHODS: All patients who underwent FS-LASIK surgery at CMU LASIK Center between January 2013 and May 2016 were retrospective reviewed. Preoperative and intraoperative data including keratometry, white-to-white (WTW) corneal diameter, flap parameters (diameter, thickness, hinge position, and tunnel length) and pulse energy were reviewed and compared between incident group and control group. To determine the risk factors, univariate and multivariate conditional logistic regression were used; the eye was unit of analysis. RESULTS: The incidence of AC gas bubbles was 1.6% (22 out of 1378 eyes). The median WTW in the AC bubbles group was 11.5 mm (range 11.1-12.1), which was significantly different from the control group (11.7 mm, range 10.5-12.8, P=0.021). The result of the median WTW minus the flap diameter in the AC bubbles group was 2.5 mm (range 2.1-3.2), which was statistically different to the control group (2.7 mm, range 1.5-3.8, P=0.008). The logistic regression analysis showed that the result of the WTW minus the flap diameter in the AC bubbles group had an adjusted odds ratio of 0.204 (95%CI; 0.056-0.747, P=0.016). CONCLUSION: Development of AC gas bubbles during FS flap creation is not an uncommon event in Asian eyes which typically have a small WTW. The flap diameter when adjusted relatively to the WTW is a predisposing factor to the possibility of AC gas bubbles occurrence.

Corneal perforation after noncontact tonometry in patients with active recurrent herpes simplex keratitis: case report.

PURPOSE: To report iatrogenic complications and to review the potential complications caused by noncontact tonometry (NCT) in related literature. METHODS: This case report describes two cases of active recurrent herpes simplex keratitis (HSK) on top of a thin corneal scar. The cornea was perforated by the air pulse from the NCT, resulting in an air bubble in the anterior chamber. RESULTS: Both patients were diagnosed with active recurrent necrotizing stromal HSK on top of a thinned corneal scar after previous therapeutic treatment involving tissue adhesive glue with a bandage contact lens (BCL) to treat a perforated cornea. During a follow-up visit, both patients reported similar symptoms of acute pain and fluid exuding from their eyes immediately after undergoing NCT. Slit-lamp examination revealed a perforated cornea with an intracameral air bubble. Treatment involved use of tissue adhesive glue and BCL in both cases. CONCLUSION: NCT may not be sufficiently safe in patients with active infectious keratitis, particularly in cases where the cornea is relatively thin and necrotic.

Outcomes of LASIK for Myopia or Myopic Astigmatism Correction with the FS200 Femtosecond Laser and EX500 Excimer Laser Platform.

PURPOSE: To evaluate the efficacy, predictability, stability and safety of laser in situ keratomileusis (LASIK) using the FS200 femtosecond laser and EX500 excimer laser platform. METHODS: The outcomes of 254 eyes of 129 consecutive patients with myopia or myopic astigmatism who underwent full correction femtosecond laser-assisted LASIK at CMU LASIK Center were assessed. Pre-operative and post-operative parameters including manifest refraction, Uncorrected Distance Visual Acuity (UDVA), Best Corrected Distance Visual Acuity (BDVA), corneal topography and tomography were analyzed. The results between low to moderate myopia and high myopia were compared up to 12 months. RESULTS: Mean pre-operative Spherical Equivalent (SE) was -5.15±2.41 Diopters (D) (range -0.50 to -11.50 D) and -0.13±0.28 D, -0.13±0.27 D, -0.13±0.28 D and -0.14±0.30 D at 1, 3, 6, and 12 months, post-operatively. At 12 months, the propor¬tion of eyes achieving UDVA ≥ 20/20 was 90.0% and ≥20/40 was 98.8%. The proportion of eyes achieving post-operative mean SE ±0.5 D, and ±1 D was 91.3%, and 98.5%. No eyes lost more than two lines of BDVA. The low to moderate myopic group had a statistically significant better UDVA at one (p=0.017) and three months (p=0.014) but no difference at six (p=0.061) and 12 months (p=0.091). The mean post-operative SE was better in low to moderate myopic group at every follow-up visit (p=0.001, 0.007, <0.001 and <0.001). CONCLUSION: One-year clinical results of LASIK with the FS200 femtosecond laser and EX500 excimer laser showed high efficacy, predictability, stability and safety.

Anterior segment and external ocular disorders associated with HIV infections in the era of HAART in Chiang Mai University Hospital, a prospective descriptive cross sectional study.

Human immunodeficiency virus (HIV) causes impairment to the human immune system which leads to immunocompromised conditions, including ocular complications. Several important HIV-associated disorders may involve the anterior segment, ocular surface, and adnexae organ such as dry eye, blepharitis which reduce quality of life of patients. In present, potent antiretroviral therapies HAART (highly active antiretroviral therapy) has improved the length and quality of life which may lead to an increased prevalence of anterior segment ocular disorders. Hence, this study has been undertaken to identify the prevalence and associated factors of anterior segment and external ocular disorder in HIV infected patients in the era of HAART. A prospective descriptive cross sectional study was carried out in HIV positive patients conducted at the Department of Ophthalmology, Chiang Mai University Hospital, from February 2014 to October 2015. Detail history and ocular examination was carried out to examine for anterior segment and external ocular disorders. A total number of 363 patients were included for this prospective cross-sectional study. From the total of 363 patients, 123 patients had an anterior segment and external ocular disorder which account as the prevalence of 33.9%. The most common anterior segment manifestations was dry eye seen in 36 patients (9.9%), followed by posterior blepharitis (Meibomian gland dysfunction) seen in 23 patients (6.3%) and anterior blepharitis seen in 12 patients (3.3%). Other ocular complications included microvasculopathy, immune recovery uveitis, conjunctivitis, papilloma, anterior uveitis, corneal ulcer, nevus, trichiasis, molluscum contangiosum, Kaposi sarcoma, interstitial keratitis, conjunctival lymphangiectasia, dacryocystitis, vernal keratoconjunctivitis and eyelid penicilosis. In this study, the prevalance of anterior segment disorders was higher than in the preHAART era. Dry eye, blepharitis and uveitis were the top three most common anterior segment disorders in the HAART era. The statistical analysis showed no association between age, sex, CD4 count, duration of infection or receiving HAART and anterior segment disorders. Anterior segment abnormalities reduce the quality of life of patients, so ophthalmologists have to be aware and complete ocular examination should be performed in all HIV infected patients.

Identification of novel PIKFYVE gene mutations associated with Fleck corneal dystrophy.

PURPOSE: To report the identification of a novel frameshift mutation and copy number variation (CNV) in PIKFYVE in two probands with fleck corneal dystrophy (FCD). METHODS: Slit-lamp examination was performed to identify characteristic features of FCD. After genomic DNA was collected, PCR amplification and automated sequencing of all 41 exons of PIKFYVE was performed. Using genomic DNA, quantitative PCR (qPCR) was performed to detect CNVs within PIKFYVE. RESULTS: In the first FCD proband, numerous panstromal punctate opacities were observed in each of the proband's corneas, consistent with the diagnosis of FCD. Screening of PIKFYVE demonstrated a novel heterozygous frameshift mutation in exon 19, c.3151dupA, which is predicted to encode for a truncated PIKFYVE protein, p.(Asp1052Argfs*18). This variant was identified in an affected sister but not in the proband's unaffected mother or brother or 200 control chromosomes. The second FCD proband presented with bilateral, discrete, punctate, grayish-white stromal opacities. Exonic screening of PIKFYVE revealed no causative variant. However, CNV analysis demonstrated the hemizygous deletion of exons 15 and 16. CONCLUSIONS: We report a novel heterozygous frameshift mutation (c.3151dupA) and a CNV in PIKFYVE, representing the first CNV and the fifth frameshift mutation associated with FCD.

Concomitant herpes simplex virus and cytomegalovirus endotheliitis in immunocompetent patient.

A case of an immunocompetent 51-year-old healthy man with chronic recurrent disciform corneal oedema and hypertensive anterior uveitis in the right eye for 2 years was unresponsive to topical corticosteroid and systemic acyclovir. Diagnostic anterior chamber tapping was performed and viral DNA PCR was positive for both cytomegalovirus and herpes simplex virus. The patient was treated with both oral valganciclovir for 3 months and long-term oral acyclovir. His condition improved significantly after the treatment; intraocular pressure and anterior chamber inflammation were controlled and the remaining keratic precipitates in the cornea started to clear up.

Causes of visual acuity loss among HIV-infected patients with cytomegalovirus retinitis in the era of highly active antiretroviral therapy in Chiang Mai University Hospital.

OBJECTIVE: To quantify the frequencies of the common causes of visual acuity loss for HIV-infected patients with cytomegalovirus retinitis (CMVR) in the era of highly active antiretroviral therapy(HAART). MATERIAL AND METHOD: The present prospective observational study comprised 113 patients (184 eyes) with newly diagnosed CMVR, from May 2008-March 2010. Each patient was followed-up every 3 months with medical history and ophthalmologic examination. Patients were divided as visual impairment and legal blindness. RESULTS: The majority of the patients were native Thai (91%), while the rest was of hill tribe origin. 55% were females with age ranged between 14-57 years (average of 39). The main cause of HIV infection was heterosexual contact (90%), followed by homosexual contact (7%). It was found that 68% had CD4 T-cell count less than 50 cells/microl and that 46% had bilateral CMVR. Major causes of visual impairment were CMVR zone 2&3, CMVR zone 1 and cataract, respectively. Major causes of legal blindness were CMVR zone 2&3, CMVR zone 1 and retinal detachment, respectively Retinal detachment was a major risk factor in both groups. Even when surgery was successful, the visual acuity was not significantly improved, indicating a permanent loss of vision. CONCLUSION: In the HAART era, immune recovery of HIV patients also helps restoring specific anti-CMVimmunity. HAART reduces occurrence of visual impairment to 0.10/eye-year (EY) and legal blindness to 0.15/EY, compared to the pre-HAART figures of 0.94-0.98/EY and 0.47-0.49/EY respectively. However, it did not completely eliminate the occurrence. CMVR and cataract remain the most common causes of visual acuity loss followed by retinitis-related retinal detachment, and optic nerve atrophy respectively.