Primary Angle Closure Observed During a House Visit: A Case Treated With Laser Iridotomy.

Laser iridotomy (LI) is an effective treatment for patients with pupillary block mechanisms. Here, we report a case of LI performed on a patient with primary angle closure (PAC) and elevated intraocular pressure (IOP), who was unsuitable for other treatments due to specific social circumstances. The patient, a 97-year-old female residing in a private nursing home, had a medical history notable only for mild dementia and was wheelchair-bound. She had not undergone ophthalmologic evaluation for over 50 years. The patient presented with intermittent tenderness and redness in the left eye. Therefore, an ophthalmologist visited the nursing home. Examination revealed visual acuity of 20/200 in the right eye and 20/100 in the left eye, IOP of 24 mmHg in the right eye and 26 mmHg in the left eye, no conjunctival hyperemia, shallow anterior chambers, and nuclear sclerosis grade 4 cataracts in both eyes. Fundus examination was challenging due to lens opacity, and both optic nerve papillae appeared pale. Given her history of episodic eye pain and hyperemia, PAC was diagnosed. Treatment options, including eye drops and cataract surgery, were discussed. However, the patient opted for LI due to her advanced age and inability to attend frequent follow-up visits. LI was successfully performed on both eyes during her visit to the clinic. One week post-procedure, IOP decreased to 12 mmHg bilaterally, with no complications. This case demonstrates that LI can be a viable option for managing PAC and high IOP in patients who are not candidates for surgery or eye drops due to social constraints.

The Necroptosis Pathway Is Upregulated in the Cornea in Mice With Ocular Graft-Versus-Host Disease.

Purpose: To identify molecular signatures specific for ocular graft-versus-host disease (GVHD) by proteomic analysis of corneas from mice with GVHD. Methods: We identified differentially expressed proteins (DEPs) in corneal samples from GVHD model mice and syngeneic control mice 4 weeks after bone marrow transplantation. Data-independent acquisition analysis was performed on individual samples, and the roles of DEPs in biological pathways related to GVHD were evaluated via bioinformatics and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results: Three important signaling pathways were upregulated in the cornea in mice with GVHD: (1) the necroptosis pathway, (2) the mitogen-activated protein kinase (MAPK) pathway, and (3) as previously reported, the neutrophil extracellular trap (NET) pathway. In those signaling pathways, we identified new upregulated molecules, including (1) receptor-interacting protein kinase 1 (RIPK1), RIPK3, interferon regulatory factor 9, the interferon-induced double-stranded RNA-activated protein kinase lipoxygenase, and high mobility group box1 (HMGB1) which are damage-associated molecular patterns (DAMPs) in the necroptosis pathway; (2) the sequentially upregulated interleukin 1 (IL-1) receptor-associated kinase (IRAK), an evolutionarily conserved signaling intermediate in the Toll pathway (ECSIT), and p38, which is downstream of the IL-1 receptor and increased CDC42/Rac (Rac2), a Rho family GTPase in the MAPK pathway; and (3) the integrin components CR3 and macrophage-1 antigen (MAC-1), which are DAMPs, and the pyroptosis-related protein gasdermin D (GSDMD) in the NET pathway. Conclusions: These novel molecules may help researchers elucidate the pathogenesis of GVHD and identify new therapeutic targets for corneal changes in patients with ocular GVHD.

A Case of Traumatic Hyphema Diagnoses by Telemedicine Between a Remote Island and the Mainland of Tokyo.

Chichijima Island, part of the Ogasawara Islands in Tokyo, is a remote island with a population of approximately 2,000, served by a few resident general practitioners (GPs). This case report discusses the application of teleophthalmology in managing pediatric ocular trauma on this remote island. A pediatric patient sustained an ocular injury from a badminton shuttlecock and was initially examined by a resident GP using a recordable slit-lamp microscope. The ocular images were transmitted to a mainland ophthalmologist through a telemedicine system. The specialist provided remote consultation and recommended further examination and treatment, leading to the patient's transfer to the mainland. The successful management of this case underscores the critical role of telemedicine in enhancing healthcare delivery in isolated regions. With advancements in medical technology, teleophthalmology is expected to become increasingly vital in providing specialized care in remote and underserved areas. The case highlights the importance of telemedicine in improving access to specialized medical expertise, ensuring timely and effective patient care, and potentially reducing the need for patient transfers to more equipped healthcare facilities.

Long-Term Outcomes of Phacoemulsification Surgeries at ECWA Eye Hospital: A Prospective Clinical Cohort Study.

Background: Phacoemulsification has proven to be a breakthrough technique in cataract surgery. Its popularity has grown dramatically as procedures and equipment have advanced, improving both safety and efficiency. This study presents long-term outcomes from phacoemulsification surgeries performed at the Evangelical Church Winning All (ECWA) Eye Hospital, a tertiary eye care center. Method: This prospective clinical cohort study followed standard practices for operations performed under local anesthesia. Ophthalmologists evaluated long-term outcomes and predictors of improved visual acuity after phacoemulsification cataract surgery. The visual recovery of the patients over time was evaluated, and the factors that influence the gains in vision were identified. Results: A total of 177 patients were subjected to treatment at our facilities during the study period. There were 116 male and 61 female patients, which resulted to a male-to-female ratio of 1 : 0.53. The average age of the patients was 59.18 years with a standard deviation of 11.38 years. Of the 259 eyes treated, 249 eyes (96.1%) achieved a high success rate with visual acuity of 6/6 - 6/18. Ten (10) eyes (3.9%) had moderate acuity between <6/18 and 6/60. Follow-up examinations over five years after phacoemulsification showed poor vision outcomes among old patients. The primary factor that affected improvement in visual acuity among patients was amblyopia, present in 30% of cases. Posterior capsular opacification and macular edema collectively accounted for 20% of poor vision cases, while optic atrophy, glaucoma, and retinal hemorrhage each represented approximately 10% of poor vision cases. Conclusions: The phacoemulsification approach demonstrated a highly effective restoration of vision for the vast majority, while long-term data analysis indicated the potential for age-related variability in postoperative visual gains.

Pheochromocytoma With High Adrenocorticotropic Hormone Production Capacity Without Pigmentation and Cushingoid Symptoms: A Case Report With a Literature Review.

Pheochromocytoma or paraganglioma (PPGL) originating from chromaffin cells can produce diverse hormones in addition to catecholamines, including adrenocorticotropic hormone (ACTH). In pheochromocytoma, high levels of ACTH might not result in pigmentation as typically observed in Addison's disease, and patients might not exhibit the symptoms of Cushing's syndrome, despite ACTH-dependent hypercortisolism. A 63-year-old male patient with hypertension was admitted to our facility, and computed tomography (CT) revealed a large right adrenal tumor. Despite high plasma ACTH (700-1300 pg/mL) and serum cortisol (90-100 µg/dL) levels, no physical pigmentation or Cushingoid symptoms were observed. Urinary metanephrine and normetanephrine levels reached as high as 16.0 mg and 3.2 mg, respectively. 123I-metaiodobenzylguanidine (MIBG) scintigraphy was negative. Low-dose dexamethasone paradoxically increased ACTH and cortisol levels, indicating the potential positive feedback regulation of both hormones by glucocorticoids. The patient was diagnosed with an ACTH-producing pheochromocytoma and underwent successful laparoscopic surgery to remove the adrenal tumor under the intravenous administration of a high-dose α-blocker and hydrocortisone. The levels of ACTH, cortisol, and urinary metanephrine/normetanephrine returned close to normal after tumor removal. We report a rare case of pheochromocytoma with extremely high ACTH/cortisol production but without pigmentation or Cushingoid symptoms. We also reviewed previous reports of ACTH-producing PPGL regarding the paradoxical regulation of ACTH/cortisol by glucocorticoids, pigmentation, Cushingoid symptoms, and negativity of 123I-MIBG scintigraphy.

Cellular senescence promotes meibomian gland dysfunction in a chronic graft-versus-host disease mouse model.

PURPOSE: Aging is a well-established risk factor for meibomian gland dysfunction (MGD). We previously reported an accelerated cellular senescence phenomenon in the lacrimal glands of a murine model of chronic graft-versus-host disease (cGVHD). Herein, we aimed to elucidate the relationship between cellular senescence and MGD in cGVHD mice, utilizing the senolytic agent ABT-263. METHODS: A cGVHD mouse model was established through allogeneic bone marrow transplantation (BMT) from B10.D2 to BALB/c mice. Subsequently, cGVHD mice were treated with either ABT-263 or vehicle. The eyelids of recipients were analyzed at 4-week intervals post-BMT in both groups. RESULTS: Meibomian gland (MG) area was significantly smaller in cGVHD mice than in syngeneic control mice. ABT-263-treated mice retained a significantly larger MG area than their vehicle-treated counterparts. Pathological and immunohistochemical examinations revealed significant reductions in eyelid tissue inflammation and pathological fibrosis in the ABT-263 group compared to that in the vehicle-treated group. Additionally, expression of DNA damage markers, senescent cell markers, and senescence-associated secretory phenotype (SASP) factors was elevated in the eyelids of cGVHD mice compared with that in syngeneic mice. The expression of these cellular senescence-associated molecules was considerably suppressed in ABT-263-treated eyelids compared to that in vehicle-treated ones. CONCLUSIONS: Cellular senescence, along with expression of SASP factors, exhibited increased activity in the eyelids, particularly in the MGs of cGVHD mice. ABT-263 mitigated the severity of MGD. These findings highlight the potential of targeting cellular senescence as an effective approach for MGD treatment in cGVHD.

Development of the AI Pipeline for Corneal Opacity Detection.

Ophthalmological services face global inadequacies, especially in low- and middle-income countries, which are marked by a shortage of practitioners and equipment. This study employed a portable slit lamp microscope with video capabilities and cloud storage for more equitable global diagnostic resource distribution. To enhance accessibility and quality of care, this study targets corneal opacity, which is a global cause of blindness. This study has two purposes. The first is to detect corneal opacity from videos in which the anterior segment of the eye is captured. The other is to develop an AI pipeline to detect corneal opacities. First, we extracted image frames from videos and processed them using a convolutional neural network (CNN) model. Second, we manually annotated the images to extract only the corneal margins, adjusted the contrast with CLAHE, and processed them using the CNN model. Finally, we performed semantic segmentation of the cornea using annotated data. The results showed an accuracy of 0.8 for image frames and 0.96 for corneal margins. Dice and IoU achieved a score of 0.94 for semantic segmentation of the corneal margins. Although corneal opacity detection from video frames seemed challenging in the early stages of this study, manual annotation, corneal extraction, and CLAHE contrast adjustment significantly improved accuracy. The incorporation of manual annotation into the AI pipeline, through semantic segmentation, facilitated high accuracy in detecting corneal opacity.

Feasibility of Tear Meniscus Height Measurements Obtained with a Smartphone-Attachable Portable Device and Agreement of the Results with Standard Slit Lamp Examination.

PURPOSE: We aimed to evaluate the feasibility of using a novel device, the Smart Eye Camera (SEC), for assessing tear meniscus height (TMH) after fluorescein staining and the agreement of the results with measurements obtained using standard slit lamp examination. METHODS: TMH was assessed using both SEC and conventional slit lamp examination. The images were analyzed using the software ImageJ 1.53t (National Institutes of Health, Bethesda, MD, USA). A common measurement unit scale was established based on a paper strip, which was used as a calibration marker to convert pixels into metric scale. A color threshold was applied using uniform parameters for brightness, saturation, and hue. The images were then binarized to black and white to enhance the representation of the tear menisci. A 2 mm area around the upper and lower meniscus in the central eye lid zone was selected and magnified 3200 times to facilitate manual measurement. The values obtained using SEC were compared with those obtained with a slit lamp. RESULTS: The upper and lower TMH values measured using the SEC were not statistically different from those obtained with a slit lamp (0.209 ± 0.073 mm vs. 0.235 ± 0.085, p = 0.073, and 0.297 ± 0.168 vs. 0.260 ± 0.173, p = 0.275, respectively). The results of Bland-Altman analysis demonstrated strong agreement between the two instruments, with a mean bias of -0.016 mm (agreement limits: -0.117 to 0.145 mm) for upper TMH and 0.031 mm (agreement limits: -0.306 to 0.368 mm) for lower TMH. CONCLUSIONS: The SEC demonstrated sufficient validity and reliability for assessing TMH in healthy eyes in a clinical setting, demonstrating concordance with the conventional slit lamp examination.

AI-based diagnosis of nuclear cataract from slit-lamp videos.

In ophthalmology, the availability of many fundus photographs and optical coherence tomography images has spurred consideration of using artificial intelligence (AI) for diagnosing retinal and optic nerve disorders. However, AI application for diagnosing anterior segment eye conditions remains unfeasible due to limited standardized images and analysis models. We addressed this limitation by augmenting the quantity of standardized optical images using a video-recordable slit-lamp device. We then investigated whether our proposed machine learning (ML) AI algorithm could accurately diagnose cataracts from videos recorded with this device. We collected 206,574 cataract frames from 1812 cataract eye videos. Ophthalmologists graded the nuclear cataracts (NUCs) using the cataract grading scale of the World Health Organization. These gradings were used to train and validate an ML algorithm. A validation dataset was used to compare the NUC diagnosis and grading of AI and ophthalmologists. The results of individual cataract gradings were: NUC 0: area under the curve (AUC) = 0.967; NUC 1: AUC = 0.928; NUC 2: AUC = 0.923; and NUC 3: AUC = 0.949. Our ML-based cataract diagnostic model achieved performance comparable to a conventional device, presenting a promising and accurate auto diagnostic AI tool.

Eye Washing Downregulated Angiotensin-Converting Enzyme 2 in Conjunctival Tissue Samples from Smokers.

This study aimed to (1) determine whether the expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 is increased in tobacco smokers, which potentially increases their susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and (2) assess whether eye rinsing can reduce susceptibility. This prospective study included 20 eyes of 10 smokers and 18 eyes of nine healthy non-smokers (control) for reverse-transcription polymerase chain reaction. This study also included 28 eyes of 14 smokers and 16 eyes of eight healthy non-smokers (control) for enzyme-linked immunosorbent assay. Tear and impression cytology samples were collected from the right eye of each patient. The left eye was then rinsed for 30 s, and after 5 min, the tear and impression cytology samples were collected in the same manner. The expression of the ACE2 gene was significantly higher in the conjunctiva of smokers (n = 17; median 3.07 copies/ng of total RNA) than in those of non-smokers (n = 17; median 1.92 copies/ng of total RNA, p = 0.003). Further, mRNA expression and protein levels of ACE2 were weakly correlated in smokers (r = 0.49). ACE2 protein levels in Schirmer's strip samples were significantly reduced from 5051 to 3202 pg/mL after eye washing (n = 10; p = 0.001). Ocular surface cells are susceptible to SARS-CoV-2 infection. Smoking may be a risk factor for SARS-CoV-2 infection, and eye rinsing may reduce the risk of infection.

Interobserver Reliability of Tear Break-Up Time Examination Using "Smart Eye Camera" in Indonesian Remote Area.

Introduction: Dry eye disease (DED) is a multifactorial disease of tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability leading to decrease of vision, productivity and quality of life, and blindness. DED diagnosis remains difficult and underdiagnosed regarding inconsistency between subjective symptoms and clinical findings. Tear break-up time (TBUT) is an objective indicator of tear film stability in diagnostic DED. A novel smartphone attachment, namely SEC (smart eye camera), could mimic conventional slit lamp to assess TBUT and beneficial in facilitating DED diagnosis. Reliability between a non and an ophthalmologist in TBUT assessment and DED diagnosis is observed in this study. Purpose: To determine interobserver reliability of TBUT measurement for diagnosing DED using SEC. Design: This a cross-sectional analytic study involving 99 participants (198 eyes) aged 40 years who visited Pratama Gema Santi Hospital, Nusa Penida, from September 2nd to 4th, 2022, with consecutive sampling technique. Methods: Fluoresceined eyes were filmed using the SEC device and apps, continued by masked ophthalmologist and resident assessing TBUT based on the video. The primary outcome is interobserver reliability for TBUT measurement and DED diagnosis. Results: The mean age of participants was 55.22±9.78 years, 48.5% male and 51.5% female. The reliability of interobserver in assessing DED based on TBUT test is 0.78 (95% CI=0.31-1.26, P-value=0.001), and interobserver reliability in diagnosing DED based on OSDI and TBUT showed good agreement (weighted kappa=0.71). Good interobserver reliability underscores that non-ophthalmologists can diagnose DED based on TBUT video using SEC. Conclusion: SEC video has good interobserver reliability to assess TBUT for DED diagnosis. SEC can be used as one of the methods in assessing DED in limited health care facilities. The high reliability of interobserver assessment indicates that DED diagnosis using video taken with SEC may be useful for telemedicine evaluation in remote areas.

A study establishing sensitivity and accuracy of smartphone photography in ophthalmologic community outreach programs: Review of a smart eye camera.

Purpose: Diseases affecting the cornea are a major cause of corneal blindness globally. The pressing issue we are facing today is the lack of diagnostic devices in rural areas to diagnose these conditions. The aim of the study is to establish sensitivity and accuracy of smartphone photography using a smart eye camera (SEC) in ophthalmologic community outreach programs. Methods: In this pilot study, a prospective non-randomized comparative analysis of inter-observer variability of anterior segment imaging recorded using an SEC was performed. Consecutive 100 patients with corneal pathologies, who visited the cornea specialty outpatient clinic, were enrolled. They were examined with a conventional non-portable slit lamp by a cornea consultant, and the diagnoses were recorded. This was compared with the diagnoses made by two other consultants based on SEC videos of the anterior segment of the same 100 patients. The accuracy of SEC was accessed using sensitivity, specificity, PPV, and NPV. Kappa statistics was used to find the agreement between two consultants by using STATA 17.0 (Texas, USA). Results: There was agreement between the two consultants to diagnosing by using SEC. Above 90% agreements were found in all the diagnoses, which were statistically significant (P-value < 0.001). More than 90% sensitivity and a negative predictive value were found. Conclusion: SEC can be used successfully in the community outreach programs like field visits, eye camps, teleophthalmology, and community centers, where either a clinical setup is lacking or ophthalmologists are not available.

Artificial intelligence to estimate the tear film breakup time and diagnose dry eye disease.

The use of artificial intelligence (AI) in the diagnosis of dry eye disease (DED) remains limited due to the lack of standardized image formats and analysis models. To overcome these issues, we used the Smart Eye Camera (SEC), a video-recordable slit-lamp device, and collected videos of the anterior segment of the eye. This study aimed to evaluate the accuracy of the AI algorithm in estimating the tear film breakup time and apply this model for the diagnosis of DED according to the Asia Dry Eye Society (ADES) DED diagnostic criteria. Using the retrospectively corrected DED videos of 158 eyes from 79 patients, 22,172 frames were annotated by the DED specialist to label whether or not the frame had breakup. The AI algorithm was developed using the training dataset and machine learning. The DED criteria of the ADES was used to determine the diagnostic performance. The accuracy of tear film breakup time estimation was 0.789 (95% confidence interval (CI) 0.769-0.809), and the area under the receiver operating characteristic curve of this AI model was 0.877 (95% CI 0.861-0.893). The sensitivity and specificity of this AI model for the diagnosis of DED was 0.778 (95% CI 0.572-0.912) and 0.857 (95% CI 0.564-0.866), respectively. We successfully developed a novel AI-based diagnostic model for DED. Our diagnostic model has the potential to enable ophthalmology examination outside hospitals and clinics.

Pediatric chronic graft-versus-host disease-related dry eye disease and the diagnostic association of potential clinical findings.

Pediatric graft-versus-host-disease (GVHD)-related dry eye disease (DED) is often overlooked due to a lack of subjective symptoms and reliable testing, leading to irreversible corneal damage. To study the clinical findings contributing to the accurate detection of pediatric GVHD-related DED, a retrospective study of pediatric patients treated with hematopoietic stem cell transplantation (HSCT) at Keio University Hospital between 2004 and 2017 was conducted. Association and diagnostic values of ophthalmological findings for DED were analyzed. Twenty-six patients who had no ocular complications before HSCT were included in the study. Eleven (42.3%) patients developed new-onset DED. The cotton thread test showed excellent diagnostic accuracy in detecting DED (area under the receiver operating curve, 0.96; sensitivity, 0.95; specificity, 0.85) with a cut-off of 17 mm, which was higher than the conventional threshold of 10 mm. Additionally, the presence of filamentary keratitis (FK) and pseudomembranous conjunctivitis (PC) were significantly associated with the diagnosis of DED (p value, 0.003 and 0.001 for FK and PC, respectively) and displayed good diagnostic performance (sensitivity, 0.46 and 0.54; specificity, 0.97 and 0.97 for FK and PC, respectively). In conclusion, the cotton thread test with a new threshold, the presence of PC and FK, could be helpful for promptly detecting pediatric GVHD-related DED.

Multicenter prospective validation study for international chronic ocular graft-versus-host disease consensus diagnostic criteria.

PURPOSE: To validate the international chronic ocular graft-versus-host disease (GVHD) diagnostic criteria (ICCGVHD) compared to the National Institute of Health diagnostic criteria 2014 (NIH2014) for chronic ocular GVHD. METHODS: Between 2013 and 2019, the study enrolled 233 patients with or without chronic ocular GVHD combined with the presence or absence of systemic chronic GVHD in an internationally prospective multicenter and observational cohort from 9 institutions. All patients were evaluated for four clinical parameters of ICCGVHD. RESULTS: The relation between the ICCGVHD score (0-11) and NIH2014 eye score (0-4) was relatively high (r = 0.708, 95% CI: 0.637-0.767, p < 0.001). The sensitivity and specificity of ICCGVHD for NIH 2014 for 233 patients were 94.3% (95% CI: 89.6%-98.1%) and 71.7% (95% CI: 63.0-79.5%), respectively (cutoff value of the ICCGVHD score = 6). The positive predictive value was 77.1% (95% CI: 71.1%-82.1%), and the negative predictive value was 87.0% (95% CI:81.6-92.5%). For the patients with systemic GVHD (n = 171), the sensitivity and specificity were 94.2% and 67.2%, respectively (ICCGVHD-score cutoff value = 6). By receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) was 0.903 (95% CI: 0.859-0.948). For patients without systemic GVHD (n = 62), the sensitivity and specificity were 100% and 76.7%, respectively (ICCGVHD-score cutoff value = 6). The AUC was 0.891 (95% CI 0.673-1.000). CONCLUSIONS: Good sensitivity, specificity, predictive value and correlation were found between ICCGVHD and NIH2014. ICCGVHD scores ≥6 can be useful to diagnose ocular GVHD with or without systemic GVHD for clinical research.

Ocular infestation by a juvenile leech, Myxobdella sinanensis in Japan.

PURPOSE: The case of ocular infestation by a leech is rare. We reported that Myxobdella sinanensis infests conjunctiva. OBSERVATIONS: A 5-year-old girl presented with blood clots in the inner corner of the left eye, and a history bloody eye discharge and bloody tears for 5 days. She was prescribed 0.5% levofloxacin ophthalmic drops for conjunctival damage. However, her parent watched a worm moving in her conjunctiva while taking a bath. She presented again the same day, and a worm was found in the left eye of the lower conjunctival fornix and was adsorbed to the inner corner. We removed a worm under eye drop anesthesia, the next day the patient had no symptoms. We captured the worm, and it was identified morphologically and genetically as Myxobdella sinanensis. This was the first case reported of Myxobdella sinanensis be infestation in a human. CONCLUSIONS AND IMPORTANCE: The ecological trait of Myxobdella sinanensis still did not remain clear, so this case report was helpful to find out a life cycle of Myxobdella sinanensis. As the outdoor population continues to increase, the cases of human parasites such as leech are expected to increase. When a patient with bloody eye discharge and bloody tears presents, we should carefully examine the conjunctiva and ocular surfaces, and interview recent history of exposure to stream water.

Eyelid blood vessel and meibomian gland changes in a sclerodermatous chronic GVHD mouse model.

PURPOSE: To investigate pathological changes in blood vessels and meibomian glands (MGs) in the eyelids of sclerodermatous chronic graft-versus-host disease (cGVHD) model mice. METHODS: We used an established major histocompatibility complex compatible, multiple minor histocompatibility antigen-mismatched sclerodermatous cGVHD mouse model. Blood vessels and MGs of eyelids from allogeneic bone marrow transplantation (allo-BMT) recipient mice and syngeneic bone marrow transplantation (syn-BMT) recipient mice were assessed by histopathology, immunohistochemistry and transmission electron microscopy. Peripheral blood samples from the recipients were examined by flow cytometry. RESULTS: Allo-BMT samples showed dilating, tortuous and branching vessels and shrunk MGs in the eyelids; showed significantly higher expression of VEGFR2 (p = 0.029), CD133 (p = 0.016), GFP (p = 0.006), and α-SMA (p = 0.029) in the peripheral MG area; showed endothelial damage and activation, fibrotic change, and immune cell infiltration into MGs compared with syn-BMT samples. Fewer Ki-67+ cells were observed in allo- and syn-BMT samples than in wild-type samples (p = 0.030). Ultrastructural changes including endothelial injury and activation, fibroblast activation, granulocyte degranulation, immune cell infiltration into MGs, and necrosis, apoptosis of MG basal cells were found in allo-BMT samples compared with syn-BMT samples. CONCLUSION: A series of our studies indicated that cGVHD can cause eyelid vessel and MGs changes, including endothelial injury and activation, neovascularization, early fibrotic changes, immune cell infiltration, MG basal cell necrosis and apoptosis, and resultant MG atrophy.