Delayed Diagnosis of Ocular Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation.

PURPOSE: To investigate the delayed diagnosis of chronic ocular graft-versus-host disease (coGVHD) after allogeneic hematopoietic stem cell transplantation (alloHCT), and further analyze potential confounding factors. METHODS: This cross-sectional study included 118 patients newly diagnosed as coGVHD after alloHCT at Zhongshan Ophthalmic Center, Sun Yat-sen University. All participants finished the flow path of medical history taking, detailed ophthalmological examination and questionnaire-based survey. coGVHD was diagnosed and graded by International Chronic Ocular GVHD Consensus Group (ICOGCG) criteria. Lag time of diagnosis was defined as interval between noting of ocular symptoms and confirmed diagnosis of coGVHD (TN-D). We further compared the clinical parameters between groups categorized by the median TN-D as medium and long delay groups. RESULTS: The median TN-D was 6.3 [IQR 2.8-14.5] months. Most coGVHD patients underwent delayed diagnosis of coGVHD longer than 3 months (70%, 83 of 118), with 90 of 118 diagnosed as severe coGVHD (76%). The long delay group exhibited higher ICOGCG scores (10 [IQR 9-10.5] vs. 9 [IQR 8-10], P=0.039) and more pronounced ocular signs, including conjunctival injection, meibomian gland loss, fibrotic tarsal conjunctiva, symblepharon, and corneal complications (all P <0.05). Delayed diagnosis was strikingly correlated with seeking ophthalmic medical care twice or more prior to diagnosis (adjusted OR=5.42, 95%CI: 1.40-21.06, P=0.015) and accurate knowledge of ocular discomfort symptoms in coGVHD (adjusted OR=0.29, 95%CI: 0.08-1.00, P=0.050). CONCLUSIONS: Delayed diagnosis of coGVHD, associated with disease severity, was common among alloHCT recipients in southern China. Improving patient education and the awareness of ophthalmologists may facilitate early diagnosis of coGVHD.

Oleic acid induces lipogenesis and NLRP3 inflammasome activation in organotypic mouse meibomian gland and human meibomian gland epithelial cells.

The accumulation of oleic acid (OA) in the meibum from patients with meibomian gland dysfunction (MGD) suggests that it may contribute to meibomian gland (MG) functional disorder, as it is a potent stimulator of acne-related lipogenesis and inflammation in sebaceous gland. Therefore, we investigate whether OA induces lipogenesis and inflammasome activation in organotypic cultured mouse MG and human meibomian gland epithelial cells (HMGECs). Organotypic cultured mouse MG and HMGECs were exposed to OA or combinations with specific AMPK agonists 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). Lipogenic status, ductal keratinization, squamous metaplasia, NLRP3/ASC/Caspase-1 inflammasome activation, proinflammatory cytokine IL-1ß production, and AMPK pathway phosphorylation in MG were subsequently examined by lipid staining, immunofluorescence staining, immunohistochemical staining, ELISA assay, and Western blot analyses. We found that OA significantly induced lipid accumulation, ductal keratinization, and squamous metaplasia in organotypic cultured MG, as evidenced by increased lipids deposition within acini and duct, upregulated expression of lipogenic proteins (SREBP-1 and HMGCR), and elevation of K10/Sprr1b. Additionally, OA induced NLRP3/ASC/Caspase-1 inflammasome activation, cleavage of Caspase-1, and production of downstream proinflammatory cytokine IL-1ß. The findings of lipogenesis and NLRP3-related proinflammatory response in OA-stimulated HMGECs were consistent with those in organotypic cultured MG. OA exposure downregulated phospho-AMPK in two models, while AICAR treatment alleviated lipogenesis by improving AMPK/ACC phosphorylation and SREBP-1/HMGCR expression. Furthermore, AMPK amelioration inhibited activation of the NLRP3/ASC/Caspase-1 axis and secretion of IL-1ß, thereby relieving the OA-induced proinflammatory response. These results demonstrated that OA induced lipogenic disorder and NLRP3 inflammasome activation in organotypic cultured mouse MG and HMGECs by suppressing the AMPK signaling pathway, indicating OA may play an etiological role in MGD.

Urban Particulate Matter Triggers Meibomian Gland Dysfunction.

Purpose: The meibomian gland (MG), as the largest modified sebaceous gland, is potentially damaged by urban particulate matter (UPM) based on epidemiological evidence, but the specific experimental mechanisms remain unknown. This study investigated the effects of UPM on MG dysfunction (MGD) in rodent models. Methods: Female C57BL/6J mice received eye drops containing UPM suspension or PBS for 14 days. The proliferative capacity and progenitor of MG were evaluated by immunofluorescence. Cell apoptosis was confirmed by TUNEL assay, along with the analysis of caspase family expression. Lipid accumulation was visualized by Oil Red O staining and LipidTox staining. Ductal hyperkeratinization, neutrophil infiltration, and pyroptosis activation were detected through immunostaining. The relative gene expression and signaling pathway activation were determined by Western blot analysis. Results: Administration of UPM caused MGD-like clinical signs, manifested as distinct corneal epithelial erosion, increased MG orifice occlusion, and glandular dropout. UPM exposure significantly induced progenitor loss, cellular apoptosis, and lipogenic disorder in MG, by reducing P63/Lrig1 expression and increasing cleaved caspase-8, -9, and -3 and meibum lipogenic protein (HMGCR/SREBP-1) expression. UPM-treated mice exhibited ductal hyperkeratinization and neutrophil recruitment. Simultaneously, pyroptosis was motivated, as indicated by the heightened expression of NLRP3 and the cleavage of caspase-1 and -4 and gasdermin D, as well as the increase in IL-1ß and IL-18 downstream. The underlying pathological mechanisms of UPM involve the phosphorylation of mitogen-activated protein kinase and nuclear factor-κB. Conclusions: These results provided direct evidence for the toxicity of UPM in MG. UPM-induced activation of pyroptosis and mitogen-activated protein kinase/nuclear factor-κB signaling pathway might account for the inflammatory MGD.

Sleep Quality in Patients With Ocular Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation.

OBJECTIVES: To investigate the sleep quality in patients with ocular graft-versus-host disease (oGVHD) compared with patients without oGVHD after allogeneic hematopoietic stem cell transplantation (alloHCT) and healthy controls. METHODS: This cross-sectional study analyzed 142 patients after alloHCT including 94 patients with oGVHD and 48 without. Fifty healthy controls were also enrolled. oGVHD was diagnosed according to International Chronic Ocular GVHD Consensus Group (ICOGCG) criteria. Sleep quality was assessed by the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI). Poor sleep quality was defined as CPQSI score greater than 6. RESULTS: Patients after alloHCT demonstrated a significantly higher CPQSI score than those of controls {7.0 [interquartile range (IQR) 5.0-10.0] vs. 5.5 [IQR 4.8-7.0], P =0.002}, especially in the oGVHD subgroup (7.5 [IQR 5.0-11.0] vs. 6.0 [IQR 5.0-8.0], P =0.04) with nearly double prevalence of poor sleep quality (58 [62%] vs. 18 [37%], P =0.006). Poor sleep quality was strikingly correlated with oGVHD diagnosis (adjusted odds ratio [OR]=2.55, 95% confidence interval [CI]: 1.02-6.34, P =0.04) and systemic immunosuppressants (adjusted OR=2.61, 95% CI: 1.32-5.71, P =0.02). Among the ocular parameters, poor sleep quality was significantly associated with higher ICOGCG score (adjusted OR=1.20, 95% CI: 1.03-1.39, P =0.02) and lower tear film break-up time (adjusted OR=0.85, 95% CI: 0.74-0.99, P =0.05). CONCLUSIONS: Poor sleep quality was associated with an increased severity of oGVHD and tear film instability in the long-term alloHCT survivorship.

Therapeutic Efficacy and Safety of Intense Pulsed Light for Meibomian Gland Dysfunction in Patients with Chronic Ocular Graft-Versus-Host Disease.

PURPOSE: To evaluate the efficacy and safety of intense pulsed light combined with meibomian gland expression (IPL-MGX) for treating meibomian gland dysfunction (MGD) associated with chronic ocular graft-versus-host disease (oGVHD). METHODS: This retrospective study included 18 patients (18 eyes) with Fitzpatrick skin type ≤ IV, who underwent 3 to 8 sessions of IPL-MGX. Dry eye symptomology, ocular surface parameters, and adverse events were evaluated. RESULTS: Of 18 eyes, 83.3% and 66.7% showed severe oGVHD and severe MGD, respectively. At 4 weeks after the final session, significant improvements in the OSDI (P < 0.001), SPEED (P = 0.001), meibum expressibility (P < 0.001), and meibum quality (P = 0.016) were observed. At 12 weeks after, the OSDI (P = 0.009), SPEED (P = 0.002), and meibum expressibility (P = 0.008) significantly improved. No adverse events owing to IPL were reported. CONCLUSION: IPL-MGX may improve the ocular symptoms, ameliorate meibomian gland secretion, and is considered as a safe treatment for MGD in oGVHD patients.

Alteration of Meibum Lipidomics Profiling in Patients With Chronic Ocular Graft-Versus-Host Disease.

Purpose: To investigate the characteristics of the lipid profiling in meibum of patients with chronic ocular graft-versus-host disease (coGVHD) and to detect the potential influence of anti-inflammatory therapy on these differential lipids. Methods: This cross-sectional study included 25 coGVHD patients and 13 non-coGVHD after allogeneic hematopoietic stem cell transplantation. Among those with coGVHD, 14 had prior topical treatment (coGVHD(T)), and 11 did not (coGVHD(WT)). All participants completed ocular surface disease index questionnaire and received slit lamp examination, Schirmer's test without anesthesia, ocular surface interferometer, and meibography. Binocular meibum was collected and pooled for lipidomic analysis by liquid chromatography-mass spectrometry. Results: One hundred and twenty differential lipid species were found among the three groups (96 of coGVHD(WT) vs. non-coGVHD, 78 of coGVHD(WT) vs. coGVHD(T), and three of non-coGVHD vs. coGVHD(T)). Compared with non-coGVHD group, coGVHD(WT) group had a significant abnormality of meibum composition, showing a significant decrease in glycerolipids, and an increase in glycerophospholipids and sphingolipids. Similar changes were also observed when coGVHD(WT) versus coGVHD(T). CoGVHD severity was negatively associated with mono-unsaturated triglycerides (TG), (ß = -214.7; 95% CI, -363.9 to -65.5; P = 0.006) and poly-unsaturated TG (ß = -4019.9; 95% CI, -7758.1 to -281.6; P = 0.036). Intensity of immunosuppression was negatively associated with mono-unsaturated TG (ß = -162.4; 95% CI, -268.6 to -56.2; P = 0.004) and positively associated with phosphatidylcholine (ß = 332.0; 95% CI, 19.2-644.8; P = 0.038). Conclusions: Altered meibum in coGVHD is characterized by a decrease of glycerolipids and an increase of glycerophospholipids and may be significantly reversed by topical anti-inflammatory therapy.

Obstruction of the Tear Drainage Altered Lacrimal Gland Structure and Function.

Purpose: Orbital glands and drainage conduits are two distinct entities that constitute the lacrimal apparatus system, the malfunction of which leads to a range of ocular surface disorders. Despite the close functional relationship, how the two parts interact under pathophysiological conditions has not been directly tested. The study aims to investigate the lacrimal gland (LG) structural and functional changes upon the drainage system obstruction, thus, testing their function link. Methods: Dacryocystectomy was performed in C57BL/6 mice to create a surgical model for tear duct (TD) obstruction (STDOB). Prickle1 mutant line with congenital nasolacrimal duct dysplasia serves as a genetic model for TD obstruction (GTDOB). Alterations of the LG and the ocular surface in tear duct obstruction mice were examined. Results: STDOB and GTDOB mice showed similar ocular surface phenotypes, including epiphora, corneal epithelial defects, and conjunctival goblet cell abnormalities. At the molecular and cellular levels, aberrant secretory vesicle fusion of the LG acinar cells was observed with altered expression and localization of Rab3d, Vamp8, and Snap23, which function in membrane fusion. LG secretion was also altered in that lactoferrin, lipocalin2, and lysozyme expression were increased in both LG and tears. Furthermore, STDOB and GTDOB mice exhibited similar LG transcription profiles. Conclusions: Physical obstruction of tear drainage in STDOB or GTDOB mice leads to LG dysfunction, suggesting a long-distance interaction between the tear drainage conduits and the LG. We propose that various components of the lacrimal apparatus should be considered an integral unit in diagnosing and treating ocular surface diseases.

Effect of Anti-Allergic Therapy on Sleep Quality of Children with Allergic Conjunctivitis and Their Parents.

PURPOSE: To assess the effect of anti-allergic therapy on sleep quality of children with allergic conjunctivitis (AC) and their parents. METHODS: This prospective single-arm intervention study included 54 AC child-parent dyads. Chinese versions of the Children's Sleep Habits Questionnaire (CSHQ) and Pittsburgh Sleep Quality Index (PSQI) were used to assess the sleep quality of children and their parents, respectively. RESULTS: CSHQ and PSQI total scores were significantly decreased after treatment, with fewer children and parents reporting poor sleep quality. Part impaired sleep behaviors of children and parents can recover to the normal levels. Sleep quality improved greater in children with a severe type of AC, those with worse baseline signs, and without other allergic diseases. For both children and parents, greater improvements in sleep quality were associated with longer treatment duration and with worse baseline sleep quality. CONCLUSION: Successful management of AC improves sleep quality for both children and their parents.

Reduction of Nitroaromatics by Gold Nanoparticles on Porous Silicon Fabricated Using Metal-Assisted Chemical Etching.

In this study, we investigated the use of porous silicon (PSi) fabricated using metal-assisted chemical etching (MACE) as a substrate for the deposition of Au nanoparticles (NPs) for the reduction of nitroaromatic compounds. PSi provides a high surface area for the deposition of Au NPs, and MACE allows for the fabrication of a well-defined porous structure in a single step. We used the reduction of p-nitroaniline as a model reaction to evaluate the catalytic activity of Au NPs on PSi. The results indicate that the Au NPs on the PSi exhibited excellent catalytic activity, which was affected by the etching time. Overall, our results highlighted the potential of PSi fabricated using MACE as a substrate for the deposition of metal NPs for catalytic applications.

3% diquafosol sodium eye drops in Chinese patients with dry eye: a phase IV study.

Introduction: The efficacy and safety of 3% diquafosol sodium eye drops in Chinese patients with dry eye in the real-world setting remains unclear. Methods: 3099 patients with dry eye symptoms were screened according to Asia Dry Eye Society latest recommendation. Among them, 3000 patients were enrolled for a phase IV study. We followed up with multiple clinical characteristics including corneal fluorescein staining, tear break up time, Schirmer's tests, visual acuity, intraocular pressure, and others. The follow ups were performed at baseline, 2 weeks and 4 weeks after treatment. Results: Based on the results of corneal fluorescein staining and tear break up time, all age and gender subgroups exhibited obvious alleviation of the symptoms among the patients with dry eye, and the data in elderly group showed the most significant alleviation. All the adverse drug reactions (ADRs, 6.17%) were recorded, among which 6% local ocular ADRs were included. Meanwhile, mild ADRs (91.8%) accounted for the most. Most of the ADRs (89.75%) got a quick and full recovery, with an average time at 15.6 days. 1.37% of patients dropped out of the study due to ADRs. Discussion: The use of 3% diquafosol sodium eye drop is effective and safe in the treatment of dry eye, with a low incidence of ADRs showing mild symptoms. This trial was registered at Chinese Clinical Trial Registry ID: ChiCTR1900021999 (Registration Date: 19/03/2019).

High Prevalence of Demodex Infestation is Associated With Poor Blood Glucose Control in Type 2 Diabetes Mellitus: A Cross-Sectional Study in the Guangzhou Diabetic Eye Study.

PURPOSE: The aim of this study was to investigate the association between type 2 diabetes mellitus (T2DM) and ocular Demodex mite infection. METHOD: About 381 patients with T2DM from nearby communities were enrolled, and 163 age-matched and sex-matched nondiabetic patients from the cataract clinic were included as the control group. All subjects underwent personal history and demographic data collection, ocular examination, and lash sampling, followed by microscopic identification and counting of Demodex mites. Binocular fundus photography was performed for diabetic patients. Statistical correlation between ocular Demodex infestation and T2DM and blood glucose control status was performed. RESULTS: The Demodex mite infestation rate (62.5% vs. 44.8%, P < 0.001) and count [3 (0-12) vs. 2 (0-9.6), P = 0.01], especially of Demodex brevis (18.9% vs. 4.9%, P < 0.001) [0 (0-1) vs. 0 (0-0), P < 0.001], were significantly higher in the T2DM patient group than that in the control group. The ratio of Demodex brevis to Demodex folliculorum in the T2DM patient group was significantly higher than that in the control group (1:3 vs. 1:9, P < 0.001). Diabetic patients presented with more cylindrical dandruff (55.1% vs. 39.3%, P = 0.001). Ocular Demodex infestation was strongly associated with poor blood glucose control (HbA 1 c > 7%) (odds ratio = 1.82; 95% confidence interval, 1.12-2.94; P = 0.2) and female sex (odds ratio = 1.69, 95% confidence interval, 1.08-2.65, P = 0.02). No association was found between Demodex infestation and the severity of diabetic retinopathy. CONCLUSIONS: Patients with T2DM, especially those with poor blood glucose control, tend to have a higher prevalence of ocular Demodex infestation, suggesting that high blood glucose is a risk factor for demodicosis .

Early detection of visual impairment in young children using a smartphone-based deep learning system.

Early detection of visual impairment is crucial but is frequently missed in young children, who are capable of only limited cooperation with standard vision tests. Although certain features of visually impaired children, such as facial appearance and ocular movements, can assist ophthalmic practice, applying these features to real-world screening remains challenging. Here, we present a mobile health (mHealth) system, the smartphone-based Apollo Infant Sight (AIS), which identifies visually impaired children with any of 16 ophthalmic disorders by recording and analyzing their gazing behaviors and facial features under visual stimuli. Videos from 3,652 children (≤48 months in age; 54.5% boys) were prospectively collected to develop and validate this system. For detecting visual impairment, AIS achieved an area under the receiver operating curve (AUC) of 0.940 in an internal validation set and an AUC of 0.843 in an external validation set collected in multiple ophthalmology clinics across China. In a further test of AIS for at-home implementation by untrained parents or caregivers using their smartphones, the system was able to adapt to different testing conditions and achieved an AUC of 0.859. This mHealth system has the potential to be used by healthcare professionals, parents and caregivers for identifying young children with visual impairment across a wide range of ophthalmic disorders.

Effect of Anti-allergic Therapy on Quality of Life in Children with Allergic Conjunctivitis and Their Parents.

PURPOSE: To evaluate the effect of anti-allergic therapy on quality of life (QoL) in children with allergic conjunctivitis (AC) and their parents. METHODS: Prospective single-arm intervention study including 55 AC child-parent pairs. The endpoint was that AC was successfully controlled after anti-allergic therapies. The primary outcome was the change in QoL of children from baseline to endpoint as measured by the total Pediatric Quality of Life Inventory (PesdQL) score. RESULTS: The total PedsQL scores of children and parents were improved after treatment (P < .001). QoL improved greater in children with vernal keratoconjunctivitis/atopic keratoconjunctivitis, those without other allergy outside the eye, and those with lower baseline total PedsQL score. Greater improvement of parents' QoL was associated with longer treating duration, greater improvement of children's QoL, lower baseline parents' total PedsQL score, and more severe baseline children's signs. CONCLUSION: Both pediatric AC patients' and their parents 'reduced QoL were improved after anti-allergic therapy. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR2000037866.

Impaired sleep quality in children with allergic conjunctivitis and their parents.

OBJECTIVES: To investigate the sleep quality in children with allergic conjunctivitis (AC) and their parents. METHODS: Prospective, case-controlled study. Zhongshan Ophthalmic Center, a tertiary referral centre. Participants comprised 73 children aged 4-12 years with AC and their parents, and 81 healthy, age-matched children who served as controls and their parents. General information was recorded and ocular manifestations of children with AC were scored. Sleep quality of the children and parents were assessed using Children's Sleep Habits Questionnaire (CSHQ) and Pittsburgh Sleep Quality Index (PSQI). RESULTS: Children with AC and their parents had reduced sleep quality (Children's CSHQ: 48.3 ± 6.55 vs. 38.8 ± 4.63; Parental PSQI: 5.62 ± 2.12 vs. 3.40 ± 1.90, both p < 0.001) and significantly higher prevalence of poor sleep quality (CSHQ ≥ 41 in Children: 89.0% vs. 23.5%; PSQI > 7 in Parents: 18.5% vs. 1.23%, both p < 0.001). Children with AC scored worse on subcomponents of CSHQ including sleep onset delay, sleep duration, parasomnia, sleep-disordered breathing, and daytime sleepiness. Parents scored worse on subscores of PSQI including sleep duration, sleep disturbances, use of sleeping medication, and daytime sleepiness. Poor sleep quality in children with AC was associated with follicle formation (OR:3.95; 95% CI: 1.88-8.31, p < 0.001) and keratitis (OR:6.03; 95% CI: 1.29-28.3, p = 0.028). Parental poor sleep quality was associated with follicle formation (OR:7.14; 95% CI: 2.06-24.8, p = 0.002) and keratitis (OR:4.49; 95% CI: 1.27-15.9, p = 0.020) in children. CONCLUSIONS: AC has a negative association with sleep quality in children and their parents, especially in those children with severe follicle formation and keratitis. STATE THE DETAILS OF CLINICAL TRIALS: Chictr.org.cn, https://www.chictr.org.cn/showproj.aspx?proj=43511 , ChiCTR1900027486. STATEMENT OF SIGNIFICANCE: Allergic conjunctivitis is a frequently encountered problem diagnosed and managed by ophthalmologists, paediatricians, allergists, and primary care physicians and has become a major public health issue. Sleep is crucial for learning and effective development in children. Our study discovered a strong association between these two conditions. This is the first study to evaluate the association of allergic conjunctivitis and sleep quality in children and their parents. This case-controlled study found that allergic conjunctivitis had a negative impact on sleep quality not only for children but also for their parents. The findings of this study suggest a multifaceted impact of AC with sleep quality; detailed assessment of sleep quality for improved care of paediatric patients with allergic conjunctivitis would be useful.

Vision-specific and cancer-specific quality of life in ocular graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

PURPOSE: To compare the vision-specific and cancer-specific quality of life (QOL) between patients with and without ocular graft-versus-host disease (oGVHD) after allogeneic hematopoietic stem cell transplantation (alloHCT). METHODS: This cross-sectional observational study analyzed 142 patients after alloHCT including 94 patients with oGVHD and 48 without. oGVHD was diagnosed according to International Chronic Ocular GVHD Consensus Group (ICOGCG) criteria. QOL was assessed by using the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). RESULTS: Compared with non-oGVHD patients, patients with oGVHD had worse vision-specific (NEI VFQ-25: 64.3 ± 20.3 vs. 77.6 ± 19.3, P < 0.001) and cancer-specific (EORTC QLQ-C30: 59.9 ± 20.3 vs. 67.4 ± 17.5, P = 0.03) QOL, as well as impaired cognitive function (72.7 ± 22.1 vs. 82.3 ± 19.0, P = 0.01). The vision-specific QOL was significantly correlated with ICOGCG score (ß = - 1.88, 95%CI: - 3.35 to - 0.41, P = 0.01) and post-alloHCT medical expense (ß = - 5.70, 95%CI: - 10.35 to - 1.05, P = 0.02), while cancer-specific QOL was strikingly correlated with post-alloHCT medical expense (ß = - 9.91, 95%CI: - 14.43 to - 5.39, P < 0.001), frequency of ophthalmic medication (ß = - 0.93, 95%CI: - 1.64 to - 0.21, P = 0.01), education (ß = - 6.97, 95%CI: - 13.31 to - 0.62, P = 0.03), and peripheral blood stem cell use (ß = - 6.42, 95%CI: - 12.59 to - 0.25, P = 0.04). CONCLUSIONS: Patients with oGVHD experienced significant impairment in both vision-specific and cancer-specific QOL including cognitive function when compared with those without after alloHCT. Multidimensional QOL assessment should be included in the long-term alloHCT survivorship care.

Posterior segment complications and the risk factors after allogeneic hematopoietic stem cell transplantation.

PURPOSE: To study the posterior segment complications (PSC) and the risk factors in patients after allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: This cross-sectional, case-control study enroled 143 patients who received allogeneic HSCT. Comprehensive ocular examinations were performed to evaluate PSC and ocular Graft-versus-Host Disease (oGVHD). PSC was diagnosed based on the characteristic fundus findings and auxiliary examinations. Visual-evoked potential was examined in patients with unexplained visual loss and suspected visual pathway pathology (VPP). Ocular surface disease index, corneal fluorescein staining, conjunctival injection and Schirmer's test were scored to diagnose oGVHD. RESULTS: PSC was detected in 36 (25.2%) patients, while 107 (74.8%) patients were not. Among them, 102 (71.3%) patients were diagnosed with oGVHD. The most common PSC included cytomegalovirus retinitis (13/143, 9.1%) and VPP (7/143, 4.9%). Central nervous system relapse of leukaemia was detected in four out of seven cases of VPP. Patients with PSC had worse visual acuity, lower prevalence and milder severity of oGVHD, and more donors from unrelated and human leucocyte antigen (HLA)-mismatch (all P < 0.05). PSC was associated with transplant from unrelated (OR = 6.494, 95% CI: 1.635-25.794, P = 0.008) and HLA-mismatched (OR = 7.193, 95% CI: 2.829-18.291, P < 0.001) donor but not with the occurrence of systemic GVHD or oGVHD. CONCLUSIONS: PSC in post-HSCT patients was more common than previously noted, deserving the concern of ophthalmologists, especially in patients with unrelated or HLA-mismatched donors.

Ocular surface disease index questionnaire as a sensitive test for primary screening of chronic ocular graft-versus-host disease.

Background: After allogeneic hematopoietic stem cell transplantation (allo-HSCT), patients are followed up by transplant clinicians. Finding an effective primary screening method that transplant clinicians or patients can master is essential in the early referral of suspected chronic ocular graft-versus-host disease (coGVHD) to an ophthalmologist. This study investigated if the ocular surface disease index (OSDI) questionnaire could be used for coGVHD primary screening. Methods: This case-controlled, cross-sectional study enrolled 161 allo-HSCT patients. All participants completed an OSDI questionnaire and underwent a silt-lamp examination. Bulbar conjunctival injection (BCI) was assessed using torchlight, while tear volume was measured via the Schirmer test (ST). The receiver operating characteristic curve was used to evaluate the sensitivity, specificity, and cutoff values of OSDI, ST, and BCI grading. Performance comparisons of the 3 tests applied in isolation, parallel, and series were made. Results: There were 84 patients with and 77 patients without coGVHD. Compared to those without coGVHD, patients with coGVHD had significantly higher median values of OSDI, corneal fluorescein staining, conjunctival injection, conjunctival fibrosis, and meibum quality, but lower ST scores (All P values <0.001). The cutoff values for OSDI, ST, and BCI grade in the diagnosis of coGVHD were 19.4 points, 7 mm, and grade 0, respectively. The sensitivity and specificity of the tests based on the cutoff values were, respectively, 89.3% and 89.6% for OSDI, 91.7% and 59.7% for ST, and 78.6% and 70.1% for BCI. The area under the curve (AUC) value of OSDI was significantly higher than that of ST (0.931 vs. 0.826; P=0.010) and BCI grade (0.931 vs. 0.781; P<0.001). The AUC values of the combinations were lower than that of OSDI alone. Conclusions: The OSDI questionnaire can be used as a simple screening test for coGVHD as demonstrated by its high sensitivity and specificity in the transplant clinic and patients' self-monitoring. An OSDI greater than 19.4 could be considered an ophthalmology referral criterion.