Tobacco effects on ocular surface, meibomian glands, and corneal epithelium and the benefits of treatment with a lipid-based lubricant.

PURPOSE: Our aim was to evaluate the ocular surface in chronic smokers and to assess the benefit of sodium hyaluronate (SH) versus semi-fluorinated alkane (SFA) eyedrops on tear film, meibomian glands, and corneal epithelial thickness (CET). METHODS: This prospective randomized single-blinded study included smokers, who applied one eyedrop of Hyabak® on one eye (SH group) and one eyedrop of EvoTears® on the fellow eye (SFA group) 4 times daily for 2 months, and age-matched non-smokers. Ocular surface parameters, including tear film break-up time (TBUT) test and corneal fluorescein staining (CFS) score, lipid layer thickness (LLT), meibography (LipiView®), and CET measurements (Zeiss Cirrus HD-5000®), were assessed at baseline and after treatment. RESULTS: Seventy-eight eyes were included in the smokers group (39 in the SH subgroup and 39 in the SFA subgroup) and 42 eyes in the control group. At baseline, the smokers group had a higher prevalence of dry eye (100% vs 0%, p < 0.001) and of meibomian gland dysfunction (MGD) and lower CET measurements than controls (p < 0.05). TBUT, CFS, and LLT (controls vs SFA group: 64.02 ± 1.87 nm vs 49.56 ± 4.33 nm, p = 0.05) improved in the SFA subgroup after treatment, but not in the SH subgroup, and became equivalent to those of controls. Prevalence of dry eye decreased in the smokers group after treatment (controls vs SH group vs SFA group: 0% vs 12.82% vs 16.26%, p > 0.05). Meibomian gland morphological parameters and CET did not improve after treatment (p < 0.05). CONCLUSIONS: Smoking is associated with dry eye, MGD, and corneal epithelial thinning that seem to be only partially reversible with topical lubricants, preferably SFA.

Diagnosis and treatment of filamentary keratitis in a patient with Demodex infestation--an overlooked risk factor: a case report.

BACKGROUND: Filamentary keratitis is an ocular condition that is tricky to handle for the difficulty to find the underlying cause. Here we report a case of filamentary keratitis associated with Demodex infestation which highlights the importance of Demodex mites as an easily-overlooked risk factor. CASE PRESENTATION: A 63-year-old woman had recurrent symptoms of foreign body sensation and sometimes painful feelings in her left eye soon after her surgical correction of ptosis in this eye. She was then diagnosed as conjunctivitis and given antibiotic eye drops. After one week, the patient complained of aggravation of symptoms with small corneal filaments in the left eye under slit-lamp examination. Despite the removal of filaments and addition of topical corticosteroids and bandage contact lenses, the patient's condition persisted with enlarged filaments and severe ocular discomfort. 3 days later, eyelashes with cylindrical dandruff were noticed and Demodex infestation was confirmed by microscopic examination of these eyelashes at our clinic this time. She was asked to use tea tree oil lid scrub twice daily. After 3 weeks, her filamentary keratitis was resolved with a dramatic improvement in symptoms and signs. And no recurrence of filamentary keratitis was noticed during the one-year follow-up. CONCLUSIONS: In this case, filamentary keratitis was resolved only with treatment of Demodex infestation while conventional treatment failed. Considering the fact that Demodex infestation is a common but easily overlooked condition, it may be suggestive to take Demodex infestation into account as a risk factor of filamentary keratitis, especially in refractory cases.

Obsructive sleep apnea syndrome: is it a risk factor for ocular surface disease and ocular comorbidities?

PURPOSE: To investigate the accompanying ocular findings in patients with obstructive sleep apnea syndrome (OSAS) and evaluate the susceptibility to ophthalmological diseases. MATERIALS AND METHODS: In this cross-sectional study, qualifying study subjects were patients who had been diagnosed with severe OSAS (apnea/hypopnea index (AHI > 30/h), n = 31), and control subjects (n = 30) who had an AHI index of < 5 (as normal). General ophthalmological examination, eyelid laxity measurements, corneal topography, visual field, retinal nerve fiber layer parameters, dry eye tests were performed on the patients. RESULTS: It was observed that the two groups had similar characteristics in terms of gender, age, presence of hypertension, diabetes, and body mass index. According to eyelid laxity measurements, the incidence of loose eyelids was higher in the OSAS patient group. Choroidal thickness was thinner in the study group than in the control group. Schirmer test and tear break-up time were significantly lower in the study group than in the control group. The percentage of meibomian gland loss in meibography and the ocular surface disease index score for symptoms was significantly higher in the study group than in the control group. CONCLUSION: In this study, we found significant changes in ocular surface parameters, eyelid laxity, choroidal thickness, and visual field indices in OSAS patients. Dry eye syndrome might be related eyelid laxity and inflammation in OSAS patients. Early diagnosis and follow-up of ocular diseases in OSAS, which affect the quality of life and visual prognosis in advanced ages, are important.

Pathophysiology of dry eye disease and novel therapeutic targets.

The pathophysiology of Dry Eye Disease (DED) is complex, and therapy may be a challenge. Tear film instability, tear film hyperosmolarity, ocular surface damage and ocular surface inflammation are accepted key events in the pathogenesis of the disease. New anti-inflammatory targets have been identified and novel anti-inflammatory treatments may enrich our therapeutic armamentarium in the future. Neurosensory changes in DED secondary to neuroinflammation in the corneal nerves, the trigeminal ganglion, and the trigeminal brainstem sensitivity complex have recently been reported and may play an important role in the pathophysiology of DED. Receptor complexes on the axonal membranes of corneal nerves may be promising novel therapeutic targets. Recent studies have shown changes in the both the systemic and local (conjunctival) microbiomes with DED as well as an association of DED with laryngopharyngeal reflux. These new insights into DED suggest new treatment approaches. In hyperevaporative DED typically associated with meibomian gland dysfunction (MGD), hyperkeratinized and obstructed meibomian glands are important treatment targets, and novel techniques may be available soon to better manage patients with MGD. The observation of changes in brain function in patients with DED sheds a completely new light on the pathophysiology of the disease. Increased understanding of the pathogenetic events described above may define novel treatment targets, guide management and may allow customized treatment of DED in the future.

Sensory neurons directly promote angiogenesis in response to inflammation via substance P signaling.

Blood vessels and nerves travel together to supply most tissues in the body. However, there is a knowledge gap in the mechanisms underlying the direct regulation of angiogenesis by nerves. In the current study, we examined the regulation of angiogenesis by sensory nerves in response to inflammation using the cornea, a normally avascular and densely innervated ocular tissue, as a model. We used desiccating stress as an inflammatory stimulus in vivo and found that sub-basal and epithelial nerve densities in the cornea were reduced in dry eye disease (DED). We established a co-culture system of trigeminal ganglion sensory neurons and vascular endothelial cells (VEC) and found that neurons isolated from mice with DED directly promoted VEC proliferation and tube formation compared with normal controls. In addition, these neurons expressed and secreted higher levels of substance P (SP), a proinflammatory neuropeptide. SP potently promoted VEC activation in vitro and blockade of SP signaling with spantide I, an antagonist of SP receptor Neurokinin-1, significantly reduced corneal neovascularization in vivo. Spantide I and siRNA knockdown of SP abolished the promotion of VEC activation by DED neurons in vitro. Taken together, our data suggested that sensory neurons directly promote angiogenesis via SP signaling in response to inflammation in the cornea.

Long-term results of topical 0.02% tacrolimus ointment for refractory ocular surface inflammation in pediatric patients.

BACKGROUND: No studies have been reported on the efficacy and safety of long-term (≥12 months) use of topical tacrolimus for refractory ocular surface inflammation in pediatric patients. METHODS: Medical records of pediatric patients who were prescribed topical 0.02% tacrolimus ointment for refractory ocular surface inflammation between January of 2010 and March of 2018 were reviewed retrospectively. Changes in ocular surface signs during slit-lamp examination, clinical symptoms and concurrent steroid use were graded with a scoring system. The presence of side effects was also assessed. The changes in disease severity and patient symptoms were compared between baseline and after the treatment. RESULTS: Among 72 patients (55% males, mean age 10.8 ± 3.9 years, range 3 to 17 years), 25 patients (48% males, mean age 11.4 ± 3.9 years) fully recovered, resulting in discontinuance of the ointment treatment before 12 months. Six patients experienced intolerable burning sensation, which required treatment cessation. Cessation days of those who quit were 1,5,14,20,26, and 35 days. Seven patients were lost during follow-up. Thirty-four patients (56% males, mean age 11.2 ± 4.2 years, range 3 to 17 years) were treated with tacrolimus ointment for over 12 months (average 23.1 ± 19.1 months, range 12 to 98 months). During the follow-up period, all patients showed improved clinical signs and symptoms, and no adverse reaction was noted. CONCLUSIONS: Long-term maintenance of topical tacrolimus 0.02% ointment is safe and effective in improving refractory ocular surface inflammation in pediatric patients.

Clinical and tear cytokine profiles after advanced surface ablation refractive surgery: A six-month follow-up.

Neuropathic dry eye is one of the most frequently seen complications after corneal refractive surgery, however, its incidence decreases in a significant manner along the first six months postoperative, reaching between 10 and 45% incidence. However, little is known on the inflammatory status of the ocular surface during this recovery process. We aim to analyze the clinical and tear molecule concentration changes along six months after advanced surface ablation for myopia correction, in a prospective study including 18 eyes of 18 subjects who bilaterally underwent advanced surface ablation corneal refractive surgery. Clinical variables (uncorrected distance visual acuity, symptoms, conjunctival hyperemia, tear osmolarity, tear stability, corneal fluorescein staining, conjunctival lissamine staining, Schirmer test, and corneal esthesiometry) and a panel of 23 pro and anti-inflammatory cytokines/chemokines concentration in tears preoperatively and at 1, 3 and 6 months postoperatively were evaluated. We found that uncorrected distance visual acuity improved significantly from baseline at 1-month visit, symptoms improved and tear osmolarity decreased significantly from baseline at 3-month visit and there was a decrease in mechanical corneal threshold between 1-month and 3- and 6-month visits. Regarding tear molecules, IL-4, IL-5, IL-6, IL-13, IL-17A, and IFN-γ tear levels were significantly increased at all the three visits, compared to preoperative levels at V0; IL-2 and VEGF were also significantly increased at 1-month and 6-month visits, but not at 3-month visit, whereas IL-9 IL-10 and IL-12 were only significantly increased at 6-month visit. Although we found that there is a recovery in clinical variables at 6 months postoperatively (i.e. neuropathic dry eye was not developed in the sample), ocular surface homeostasis is not completely restored, as it can be seen by the changes in concentration of some pro and anti-inflammatory molecules measured in tears.

Changes of tear lipid mediators after eyelid warming or thermopulsation treatment for meibomian gland dysfunction.

Meibomian gland dysfunction (MGD) represents a major cause of dry eye and ocular discomfort. Lipid mediators, often termed oxylipins, can be produced enzymatically or non-enzymatically, and may modulate inflammatory processes in MGD. Here, we aimed to assess the longitudinal changes of lipid mediators after various eyelid treatments (eyelid warming and thermopulsation) over 12 weeks. Secondly, we aimed to assess the chirality of mono-hydroxyl lipid mediators from tears of MGD and healthy participants. Tears lipid mediators were extracted from Schirmer's strips and levels were quantified by liquid chromatography mass spectrometry (LC-MS) techniques. We quantified 33 lipid mediators in the tear, 18 of which (including 11-HETE, 20-OH-LTB4, and 15-oxoETE) were reduced significantly after treatment. Changes in concentrations of 10-HDoHE (r = 0.54) and 15-oxoETE (r = 0.54) were correlated to the number of meibomian gland plugs at baseline, so increased severity of MGD was associated with treatment-induced change in lipid mediators. The chiral analysis demonstrated that 5(S)-HETE, 12(S)-HETE, 15(S)-HETE, 14(S)-HDoHE, 17(S)-HDoHE and 11(R)-HETE were produced with significant enantiomeric excess (ee %) in controls compared to patients, due to enantiomer selective enzymatic action, whereas most lipid mediators were racemates in patients, due to dominance of oxidative effects which have no enantiomeric preference. Treatment of MGD restored the concentrations of 15(S)-HETE, 14(S)-HDoHE and 17(S)-HDoHE with significant ee values, suggesting reduction in oxidative action. Overall, MGD therapy reduced pro-inflammatory molecules generated by lipoxygenase and oxidative stress.

Association of Ramadan daytime fasting with ocular surface inflammation and dry eye.

PURPOSE: Despite the widespread practice of fasting, there are no studies looking at ocular surface inflammation, specifically matrix metalloproteinase 9 (MMP-9) testing, during fasting. In this prospective study, we wanted to evaluate the effect of Ramadan fasting on the level of tear film MMP-9 as well as other standard indicators of dry eye disease. METHODS: Forty healthy patients without history of ocular disease were tested before and toward the end of Ramadan. Each patient was assessed at each timepoint for tear film MMP-9 positivity as measured by a commercially available test (InflammaDry; Quidel Corp., San Diego, CA, USA) which detects MMP-9 levels of more than 40 ng/ml. Ocular surface disease index (OSDI) scores, tear breakup time (TBUT), Schirmer I test (S1T) and corneal fluorescein staining (CFS) were also evaluated at each timepoint. RESULTS: InflammaDry was positive in 10 patients (25%) prior to Ramadan and 21 patients (52.5%) during Ramadan fasting, and this change was statistically significant (p = 0.02). Mean TBUT decreased from 7 s prior to Ramadan to 5.3 s during Ramadan fasting, and this change was statistically significant (p = 0.01). OSDI, CFS and S1T did not show any statistically significant changes (p > 0.05 for all). CONCLUSION: Ramadan fasting has a significant impact on TBUT and ocular surface inflammation detected by Inflamma Dry testing. Patients who suffer from dry eye disease and those who develop symptoms during Ramadan are advised to consult with a physician before or during Ramadan fasting.

Level of tear cytokines in population-level participants and correlation with clinical features.

AIMS: Tear cytokine levels indicate severity of ocular surface inflammation. Previous reports of cytokine concentrations were based on hospital-based studies or non-Chinese populations. We determine the range of tear concentration of cytokines in a representative adult Chinese population. METHODS: Thirty-nine participants were recruited from a population-based study of Chinese adults in Singapore, and standardized clinical ocular surface/eyelid features evaluated. Tear was extracted from Schirmer strips and analysed using a multiplex bead-based assay. RESULTS: Tear concentrations of 14 cytokines were investigated and quantifiable in each participant. Eight cytokines increased with increasing age, and 4 cytokines (IL-4, IL-12, IL-10 and IFN-γ) were increased in people with increased frequency of ocular discomfort. Three cytokines (MCP-1, IP-10 and IL-13) had increased levels in people with lower Schirmer tests, while 9 other cytokines were increased in patients with eyelid crusting (TNF-α, IL-1ß, IL-17α, IL-2, IL-4, IL-6, IL-12, IL-10 and IFN-γ). Twelve percent of participants had eyelid crusting. CONCLUSION: Using a convenient collection technique that is a routine clinical test, 14 tear cytokines could be quantifiable even in Singapore Chinese adults without a dry eye diagnosis. Elevation of different tear cytokines may be linked to subclinical aqueous tear deficiency or eyelid inflammation even in asymptomatic people.

The levels of 12 cytokines and growth factors in tears: hyperthyreosis vs euthyreosis.

PURPOSE: Simultaneous analyses of the contents and ratios of 12 cytokines and growth factors in single samples of human tears were performed, and the results were compared between a group of healthy subjects and a group of patients with Graves' hyperthyreosis (GH) without thyroid-associated orbitopathy (TAO). METHODS: Determinations and concentration measurements of interleukins (IL-2, IL4, IL-6, IL-8, IL-10, IL-1α, and IL-1ß) interferon (IFN-γ), tumor necrosis factor (TNF-α), monocyte chemoattractant protein (MCP-1), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) were performed with single tear samples from 21 patients with hyperthyreosis and 22 healthy subjects. The analyses were performed using a Randox microchip with an Evidence Biochip Array Analyzer. RESULTS: We found significant differences between the healthy donor group and the hyperthyreosis group in the levels of IL-6, IL-10, VEGF, IL-1α, and MCP-1. The concentration of IL-6 was considerably higher in the hyperthyreosis group, IL-10 was higher in the healthy donor group, and VEGF and MPC-1 were higher in the hyperthyreosis group. The IL-8 and IFN-γ levels were higher in the hyperthyreosis group. The ratios of all of the cytokines to anti-inflammatory IL-10 were significantly elevated in the hyperthyreosis group. CONCLUSION: There are clear differences in the levels of cytokines and growth factors in the tears of healthy subjects and patients with GH without TAO. Tear cytokine changes and related dysfunctional tear syndrome (DTS) could be an early sign of occult TAO in Graves' hyperthyreosis patients.

Cathepsin S Alters the Expression of Pro-Inflammatory Cytokines and MMP-9, Partially through Protease-Activated Receptor-2, in Human Corneal Epithelial Cells.

Cathepsin S (CTSS) activity is increased in tears of Sjögren's syndrome (SS) patients. This elevated CTSS may contribute to ocular surface inflammation. Human corneal epithelial cells (HCE-T cells) were treated with recombinant human CTSS at activity comparable to that in SS patient tears for 2, 4, 8, and 24 h. Acute CTSS significantly increased HCE-T cell gene and protein expression of interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) from 2 to 4 h, while matrix metalloproteinase 9 (MMP-9), CTSS, and protease-activated receptor-2 (PAR-2) were increased by chronic CTSS (24 h). To investigate whether the increased pro-inflammatory cytokines and proteases were induced by CTSS activation of PAR-2, HCE-T cells were transfected with PAR-2 siRNA, reducing cellular PAR-2 by 45%. Cells with reduced PAR-2 expression showed significantly reduced release of IL-6, TNF-α, IL-1ß, and MMP-9 into culture medium in response to acute CTSS, while IL-6, TNF-α, and MMP-9 were reduced in culture medium, and IL-6 and MMP-9 in cell lysates, after chronic CTSS. Moreover, cells with reduced PAR-2 expression showed reduced ability of chronic CTSS to induce gene expression of pro-inflammatory cytokines and proteases. CTSS activation of PAR-2 may represent a potential therapeutic target for amelioration of ocular surface inflammation in SS patients.

Ocular surface inflammation impairs structure and function of meibomian gland.

Dysfunction of the meibomian glands alters secreted meibum quantitatively and qualitatively that can lead to damage to the ocular surface epithelium. In response to an unstable tear film cause by meibomian gland dysfunction, ocular surface epithelium is damaged and expresses inflammatory cytokines leading to secondary ocular inflammation. In turn, inflammatory disorders of the palpebral conjunctiva and lid margin may affect the structure and function of meibomian gland. The disorders include allergic conjunctivitis, long-term usage of contact lenses, dermatological diseases that affect conjunctival homeostasis, Stevens-Johnson's syndrome or chemical burning of the ocular surface and lid margin.

Low Rate of Postoperative Pterygium Recurrence in Patients under Treatment with Low-Dose Oral Doxycycline for Chronic Blepharitis: A First Report.

PURPOSE: Low doses of systemic doxycycline (LD-SD) inhibit angiogenesis and the expression of matrix metalloproteases, which are determinants of pterygium progression. This study aimed to compare the recurrence rate and visual outcome of pterygium excision in patients undergoing chronic treatment with LD-SD for chronic refractory blepharitis and LD-SD-naive patients. METHODS: A retrospective analysis of patients that underwent surgical excision and conjunctival graft apposition was conducted. Patients were divided in a TETRA group (under LD-SD treatment at the moment of surgery) and a control group. The main outcome was the rate of recurrence at 1 year postoperatively. Secondary outcomes were the comparisons of surface regularity, visual quality, and dry-eye symptoms at 6-week, 6-month, and 1-year follow-up in the two groups. RESULTS: The TETRA group showed a significantly lower rate of 1-year recurrence both in primary (p = 0.034) and recurrent (p < 0.001) pterygia. The best corrected visual acuity (BCVA), astigmatic error, corneal total root mean square (RMS), and ocular surface disease index (OSDI) significantly reduced during the follow-up in both groups. The surface asymmetry index and high-order aberrations (HOAs) significantly reduced only in the TETRA group. The final BCVA was significantly higher, while the OSDI score and total RMS and HOAs were significantly lower in the TETRA group compared to the control. CONCLUSIONS: Patients under treatment with LD-SD showed a lower rate of recurrence at 1-year follow-up compared to controls. These patients also experienced higher BCVA and surface regularity and less dry-eye symptoms.

Corneal Epithelial Dendritic Cells: An Objective Indicator for Ocular Surface Inflammation in Patients with Obstructive Meibomian Gland Dysfunction?

PURPOSE: To examine whether corneal epithelial dendritic cells (CEDC) could serve as an indicator to distinguish obstructive meibomian gland dysfunction (MGD) with or without ocular surface inflammation (OSI). METHODS: We performed a case-control study on patients with diagnosed obstructive MGD between August 2017 and November 2019. RESULTS: 30 MGD cases and 25 healthy controls were recruited. The classification of MGD patients with and without OSI was based on the tear pro-inflammatory cytokine levels. Compared with the MGD without OSI and the control group, a higher CEDC density was detected in the MGD with OSI subgroup. The presence of >15.6 cells/mm2 CEDC had a sensitivity of 73% and specificity of 75% for the diagnosis of MGD with OSI. CONCLUSIONS: OSI is not present in all patients with obstructive MGD. Evaluation of CEDC density in the central cornea may help identify whether MGD is concomitant with OSI.

Management of Ocular Surface Inflammation with Persistent Epithelial Defects Using a Sutureless Human Amniotic Membrane Dehydrated Matrix: A Prospective Study Utilizing a Digital Ocular Surface Assessment Tool.

Purpose: To report the outcomes of using a sutureless human amniotic membrane dehydrated matrix (HAMDM) in the management of a range of ocular surface conditions utilizing a digital ocular surface disease assessment tool. Methods: Two UK NHS Trusts - Queen Victoria Hospital Foundation Trust (East Grinstead and Maidstone) and Tunbridge Wells Trust (Kent) - prospectively treated patients with ocular surface disease with sutureless HAMDM. The patient cohort was assessed for resolution of epithelial defects, ocular surface inflammation, and best-corrected visual acuity pre- and posttreatment. Measurements of ocular surface inflammation and epithelial defect size were assessed using AOS digital imaging software, a validated tool for objective grading of bulbar conjunctival redness and measurement of corneal epithelial defects. Results: A total of 47 applications of sutureless HAMDM on 46 eyes of 46 patients (25 male, 21 female, age 9-94 years) were assessed across various etiologies for an average of 24.0±14.1 days. Patients with limbal stem-cell deficiency (n=17), persistent epithelial defects (n=16), neurotrophic corneal disease (n=7), filamentary keratitis (n=2), corneal erosion (n=1), corneal thinning (n=1), ocular surface inflammation (n=1), and traumatic corneal laceration (n=1) were included in the study. Across all patents, 63% of eyes showed complete healing of epithelial defects and 32.6% of eyes showed partial resolution. The average rate of healing (wound closure) was 0.36 mm2 per day across the overall patient cohort, and the rate of healing in cases with complete resolution of epithelial defects was 0.41 mm2 per day. Inflammation across all four quadrants of the ocular surface remained stable. Visual acuity across the patient cohort remained stable (61%) and improved in 26% of patients (0.06±0.51 logMAR). Conclusion: Sutureless HAMDM application can be accomplished in just a few minutes and effectively treat a range of ocular surface disease in a clinical, nonsurgical setting. The AOS imaging software offered a quantitative methodology for measuring epithelial defect size and inflammation state.

Salzmann Nodular Degeneration in Ocular and Systemic Diseases.

This review aimed to evidence the predisposing conditions for Salzmann nodular degeneration (SND), where particular attention was paid to its association with ocular and systemic diseases. SND is a rare disease characterized by bluish-white nodules located in the mid-periphery of the cornea, which are otherwise completely clear. SND has been found in association with different systemic and ocular diseases, and it may have unilateral or bilateral presentation. Initial forms are only diagnosed occasionally as they are asymptomatic, whereas, in advanced disease, the visual acuity might be seriously impaired. Although SND is well described, its exact etiopathology is currently still unknown and is frequently misdiagnosed. It is associated with ocular surface inflammatory conditions and previous corneal surgery, and it has been described in different systemic diseases. Diagnosis is clinically based with slit lamp examinations, and instrumental assessments with corneal topography permit one to observe the alterations of the corneal profile, whereas anterior segment-optical coherence tomography (AS-OCT) is used to investigate the stromal depth of the nodules. Therapy might be conservative with the objective of improving the ocular surface homeostasis and surgical outcomes, where the aim is to restore the corneal regularity and visual acuity. Ophthalmologists should pay particular attention when detecting nodules in patients with ocular and non-ocular inflammatory diseases to guarantee the patient a timely diagnosis and a better therapeutic outcome. Additionally, collaboration between specialists who deal with treating patients suffering from disorders potentially associated with SND is recommended.

Effects of full-thickness wedge resection on ocular surface and in vivo confocal microscopy findings in floppy eyelid syndrome patients.

OBJECTIVE: To evaluate the effect of full-thickness wedge resection (FTWR) on ocular surface and in vivo confocal microscopy (IVCM) findings in patients with floppy eyelid syndrome (FES). METHODS: The study included two groups: a surgical treatment (ST) group (26 eyes) consisting of patients who underwent FTWR surgery, and a conservative treatment (CT) group (30 eyes). Pre-treatment and post-treatment ocular surface disease index (OSDI), tear break-up time (TBUT), corneal fluorescein staining (CFS), IVCM findings along with the body mass index (BMI), FES grade, the presence and the treatment of obstructive sleep apnea syndrome (OSAS) were recorded and compared between the groups. RESULTS: The groups were comparable in terms of BMI, FES grade, and OSAS data. After six months, TBUT in the ST group significantly increased to 12.92 ± 1.15, compared to 8.10 ± 1.60 in the CT group (p = 0.000). The CFS and OSDI scores were significantly lower in the ST group (0.15 ± 0.37, 18.0 ± 8.3, respectively) compared to the CT group (0.90 ± 0.61, 27.3 ± 9.3, respectively) (p = 0.000). IVCM analysis revealed a significant decrease in dendritic cell count (ST: 22.0 ± 12.4, CT: 39.5 ± 15.1, p = 0.000) and nerve tortuosity (ST: 1.38 ± 0.64, CT: 2.00 ± 0.59, p = 0.000), with a significant increase in total nerve density (ST: 4.27 ± 0.83, CT: 3.57 ± 0.90, p = 0.002) in the ST group compared to the CT group after six months. CONCLUSION: In our retrospective cohort, FTWR surgery was shown to be an effective and reliable surgical treatment for FES, improving both ocular surface and IVCM findings. Patients with moderate to severe stages of FES not responding to conservative treatment may benefit from eyelid tightening.

Remarkable improvement of symptoms and signs of severe dry eye treated by ocular immersion hydrotherapy.

Key Clinical Message: Traditional treatment options are often insufficient in treating severe dry eyes caused by systemic diseases. This case demonstrates that ocular immersion hydrotherapy significantly alleviated symptoms and ocular surface inflammation in ocular graft-versus-host disease. Based on these findings, we propose it as a promising option for managing severe dry eye disease. Abstract: This case report investigates the efficacy of ocular immersion hydrotherapy (OIH) in treating severe dry eye secondary to ocular graft-versus-host disease (oGVHD). A 35-year-old female with a history of acute myeloid leukemia-M2 and subsequent hematopoietic stem cell transplantation (HSCT) developed high-intensity oGVHD unresponsive to conventional treatments, including topical corticosteroids and lubricants. We introduced OIH, utilizing sterilized swimming goggles filled with intraocular irrigating solutions, providing a moist microenvironment for the ocular surface. Symptoms were significantly relieved after treatment. Corneal filaments and epithelial defects were significantly reduced, and in vivo confocal microscopy (IVCM) demonstrated resolution of inflammation and reappearance of corneal nerves. This case indicates that OIH could be a promising therapeutic approach for severe dry eye conditions arising from oGVHD, particularly for patients refractory to traditional treatments. Further studies are warranted to elucidate the long-term benefits and mechanisms of OIH in oGVHD management.

Challenges and concepts in the diagnosis and management of ocular graft-versus-host disease.

Graft-versus-host disease (GVHD) is characterized by tissue inflammation in the host following an allogeneic hematopoietic cell transplantation (HCT). The pathophysiology is complex and only incompletely understood yet. Donor lymphocyte interaction with the histocompatibility antigens of the host plays a crucial role in the pathogenesis of the disease. Inflammation may affect multiple organs and tissues, e.g., the gastrointestinal tract, liver, lung, fasciae, vaginal mucosa, and the eye. Subsequently, alloreactive donor-derived T and B lymphocytes may lead to severe inflammation of the ocular surface (i.e., cornea and conjunctiva) and the eyelids. Furthermore, fibrosis of the lacrimal gland may lead to severe dry eye. This review focuses on ocular GVHD (oGVHD) and provides an overview of current challenges and concepts in the diagnosis and management of oGVHD. Ophthalmic manifestations, diagnostic procedures, grading of severity and recommendations for ophthalmic examination intervals are provided. Management of ocular surface disease with lubricants, autologous serum eye drops, topical anti-inflammatory agents and systemic treatment options are described based on the current evidence. Ocular surface scarring and corneal perforation are severe complications of oGVHD. Therefore, ophthalmic screening and interdisciplinary treatment approaches are highly relevant to improve the quality of life of patients and to prevent potentially irreversible visual loss.