Environmental and Occupational Triggers of Dry Eye Symptoms in the Ahsa Region of Saudi Arabia: A Cross-Sectional Study.

Objective: This cross-sectional study aimed to investigate the associations between environmental and occupational factors and the prevalence of dry eye symptoms among participants from the Ahsa region of Saudi Arabia. Methods: Participants from urban, rural, and suburban areas seeking medical care at primary health centers were recruited through systematic random sampling. Data on demographics, exposures, and ocular health were captured using a structured questionnaire. Dry eye symptoms were evaluated using the Ocular Surface Disease Index (OSDI), Impact of Dry Eye on Everyday Life (IDEEL), and Symptom Assessment in Dry Eye (SANDE) questionnaires. Logistic regression analysis examined the relationships between environmental/occupational factors and the prevalence of dry eye symptoms. Results: Key exposures included particulate matter (PM) (60%), low humidity (55%), wind/dust (50%), prolonged computer use (65%), and chemical irritants (45%). These factors were significantly associated with an increased prevalence of dry eye symptoms, with the following odds ratios (ORs): PM (1.85, 95% CI: 1.35-2.52), low humidity (1.45, 95% CI: 1.05-2.00), wind and dust (1.60, 95% CI: 1.20-2.14), prolonged computer use (2.10, 95% CI: 1.55-2.85), and chemical irritants (1.75, 95% CI: 1.30-2.35). All associations were statistically significant (p < 0.05). The use of protective equipment was associated with reduced odds of dry eye symptoms (OR 0.60, 95% CI: 0.42-0.85, p = 0.03). Conclusion: This study identifies significant associations between specific environmental and occupational exposures and the prevalence of dry eye symptoms. Reducing modifiable exposures through policy, workplace enhancements, and clinical preventative strategies is essential to mitigate the burden of dry eye symptoms related to modern lifestyles and technology.

Association between insulin-like growth factor-1 and ocular surface parameters in obese prepubertal boys.

The study aimed to investigate the correlation between insulin-like growth factor 1 (IGF-1) and ocular surface parameters in obese prepubertal boys. Thirty obese prepubertal boys and 30 age- and gender-matched healthy controls underwent physical measurements, laboratory tests, and ocular surface assessments. The obese group showed lower IGF-1 levels (P = 0.001), reduced Schirmer I tear test (SIT) (P <0.001), and higher meibomian gland scores (meiboscore) compared to controls (P = 0.015). Bivariate analysis revealed a positive association between IGF-1 and SIT (r = 0.677, P < 0.001), and a negative association with between IGF-1 and meiboscore (r = - 0.487, P < 0.001). Multiple regression analysis indicated that IGF-1 (P < 0.001) and triglycerides (P = 0.028) independently influenced SIT. Logistic analysis showed a significant association between decreased IGF-1 and higher meiboscore values (OR 0.994, 95% confidence interval 0.988-1.000; P = 0.033). CONCLUSION: The findings suggest that reduced IGF-1 in obese prepubertal boys is independently linked to decreased SIT and increased meiboscore, irrespective of obesity and traditional cardiovascular risk factors. This implies that monitoring ocular surface parameters in obese children might provide a new perspective for clinical practice to focus on. WHAT IS KNOWN: • Obese children exhibit decreased levels of IGF-1, and this reduction in IGF-1 is associated with cardiovascular metabolic complications related to obesity. • Ocular surface tissues might act as targets for hormones, might experience local effects of these hormone. WHAT IS NEW: • In prepubertal obese boys, the decrease in IGF-1 is independently linked to decreased SIT and increased meiboscore, irrespective of obesity and traditional cardiovascular risk factors. • This finding implies that monitoring ocular surface parameters in obese children might provide a new perspective for clinical practice to focus on.

Biomolecule-based hydrogels as delivery systems for limbal stem cell transplantation: A review.

Limbal stem cell deficiency (LSCD) is a complex disease of the cornea resulting from dysfunction and/or loss of limbal stem cells (LSCs) and their niche. Most patients with LSCD cannot be treated by conventional corneal transplants because the donor tissue lacks the LSCs necessary for corneal epithelial regeneration. Successful treatment of LSCD depends on effective stem cell transplantation to the ocular surface for replenishment of the LSC reservoir. Thus, stem cell therapies employing carrier substrates for LSCs have been widely explored. Hydrogel biomaterials have many favorable characteristics, including hydrophilicity, flexibility, cytocompatibility, and optical properties suitable for the transplantation of LSCs. Therefore, due to these properties, along with the necessary signals for stem cell proliferation and differentiation, hydrogels are ideal carrier substrates for LSCD treatment. This review summarizes the use of different medical-type hydrogels in LSC transplantation from 2001 to 2024. First, a brief background of LSCD is provided. Then, studies that employed various hydrogel scaffolds as LSC carriers are highlighted to provide a multimodal strategic reference for LSCD treatment. Finally, an analysis of prospective future developments and challenges in the field of hydrogels as LSC carriers for treating LSCD is presented.

Effect of upper eyelid blepharoplasty surgery on cornea biomechanics and ocular surface.

PURPOSE: To evaluate the changes in corneal biomechanical properties and tear film layer analysis after upper eyelid blepharoplasty surgery. METHOD: Sixty eyes of 30 patients were included in our prospective study. Corneal hysteresis (CH), corneal resistance factor (CRF), corneal compensated intraocular pressure (IOPcc) and Goldmann intraocular pressure (IOPg) measurements were taken with the Ocular Response Analyzer (ORA) device at the preoperative, postoperative 1st and 3rd months. The ocular surface was evaluated with tear breakup time (TBUT) and Ocular Surface Disease Index (OSDI) scores. Lid crease (LC), margin-to-reflex distance 1 (MRD1), and palpebral fissure height (PFH) were evaluated at each visit. RESULTS: In the ORA analysis, in the 1st month CH value was found to be significantly lower than the preoperative value (preoperative 13.39 ± 6.08 mmHg; 1st month 10.74 ± 1.94 mmHg, p = 0.011). In addition, there was a statistically significant decrease in the 3rd month value compared to the preoperative values (10.46 ± 1.69 mmHg, p = 0.021). However CRF decreased postoperatively, no statistical difference was detected (preop 12.59 ± 3.84; 1st month 11.94 ± 3.04; 3rd month 9.78 ± 1.74; p = 0.149). While there was a decrease in IOPcc and IOPg in the postoperative period, no statistical difference was detected (respectively p = 0.96, p = 0.71). In the postoperative 1st month, TBUT increased significantly (p = 0.024). When those with a TBUT value below 10 were considered dry eye, significant decrease was observed in the percentage of dry eye in the first postoperative month (p = 0.027). Although the dry eye percentage decreased in the 3rd month compared to the preoperative percentage, no statistical difference was detected (p = 0.125). There was a significant decrease in the number of those with an OSDI score above 13 in the first month (p = 0.004). CONCLUSION: In our study, a decrease in ORA values was observed after blepharoplasty, with only CH being statistically significant. Reducing the load on the cornea after surgery may change the corneal biomechanics. These changes should be taken into consideration after eyelid surgery, especially in patients who may require glaucoma follow-ups.

Construction of living-cell tissue engineered amniotic membrane for ocular surface disease.

BACKGROUND: Human amniotic membrane (AM) transplantation has been applied to treat ocular surface diseases, including corneal trauma. The focus of much deliberation is to balance the mechanical strength of the amniotic membrane, its resistance to biodegradation, and its therapeutic efficacy. It is commonly observed that the crosslinked human decellularized amniotic membranes lose the functional human amniotic epithelial cells (hAECs), which play a key role in curing the injured tissues. METHODS AND RESULTS: In this study, we crosslinked human decellularized amniotic membranes (dAM) with genipin and re-planted the hAECs onto the genipin crosslinked AM. The properties of the AM were evaluated based on optical clarity, biodegradation, cytotoxicity, and ultrastructure. The crosslinked AM maintained its transparency. The color of crosslinked AM deepened with increasing concentrations of genipin. And the extracts from low concentrations of genipin crosslinked AM had no toxic effect on human corneal epithelial cells (HCECs), while high concentrations of genipin exhibited cytotoxicity. The microscopic observation and H&E staining revealed that 2 mg/mL genipin-crosslinked dAM (2 mg/mL cl-dAM) was more favorable for the attachment, migration, and proliferation of hAECs. Moreover, the results of the CCK-8 assay and the transwell assay further indicated that the living hAECs' tissue-engineered amniotic membranes could facilitate the proliferation and migration of human corneal stromal cells (HCSCs) in vitro. CONCLUSIONS: In conclusion, the cl-dAM with living hAECs demonstrates superior biostability and holds significant promise as a material for ocular surface tissue repair in clinical applications.

Effect of autologous serum after amniotic membrane transplantation for persistent corneal ulcers.

AIM: To investigate the effect of adding autologous serum eye drops to the postoperative regime after amniotic membrane transplantation for severe persistent corneal ulcers. METHODS: Forty eyes of 40 patients with persistent corneal ulcers were randomly assigned to artificial tears (sodium hyaluronate 0.2%, ATs group, n=20) or autologous serum eye drops (ASEDs, n=20) following treatment with amniotic membrane transplantation. Digital slit lamp images were acquired from all patients before and 30d post treatment. The area with fibrovascular tissue was calculated using Image J. Central corneal sensitivity was assessed by Cochet-Bonnet aesthesiometry before and one month after treatment. Scar tissue transparency was assessed with a novel optical densitometry. RESULTS: Mean age of patients was 61.65±16.47y and 57.3±19.11y in the ATs group and ASEDs group, respectively. Twenty-two male and 18 female patients were included in the study. The improvement in visual acuity was significantly greater in the ASEDs group (0.14±0.04) than the ATs (0.08±0.04; P=0.00046). Cochet-Bonnet aesthesiometry improved significantly after treatment with a similar rate between groups. There were no statistically significant differences in the area of postoperative fibrovascular tissue between the two groups (P=0.082). The success rate in the two groups was similar. The difference in densitometry between the ATs and ASEDs group was statistically significant (P=0.042) with greater reduction from baseline in the ASEDS group. CONCLUSION: Autologous serum eye drops can lead to better visual acuity, more stable results and improved densitometry and should be considered in the postoperative care following amniotic membrane transplantation.

Secondary corneal keloid: a report of two cases.

We conducted clinical and histological evaluations on two male patients who presented with corneal keloid. One patient had a history of corneal trauma due to contact with boiling sunflower oil, while the other had undergone pterygium removal. Upon slit lamp examination, the corneal lesions were identified as single, well-circumscribed, pearly white nodules with a smooth surface. We successfully removed these nodules using a combination of superficial keratectomy and the application of mitomycin C. Light microscopy analysis of the excised nodules revealed hyperplastic epithelium, disrupted Bowman's layer, and irregularly arranged abundant collagen fibers within the stroma. Notably, there was no recurrence of the lesions in either case within six months following the surgical excision. Secondary corneal keloids should be considered as a potential diagnosis in patients with elevated corneal nodules, especially when there is a history of ocular surface trauma or surgery.

Treatment of ocular surface squamous neoplasia in an Indian rural facility: a study of 38 eyes.

PURPOSE: To report the demographic profile, clinical presentation, and management outcomes of ocular surface squamous neoplasia (OSSN) treated with primary topical chemotherapy in a limited resource secondary eye care facility in rural parts of South India. METHODS: Retrospective interventional study of 38 eyes of 37 patients with OSSN treated with topical 1% 5-Fluorouracil (5FU), over a period of two years. RESULTS: The median age at presentation with OSSN was 44 years (mean, 46 years; range 13 to 74 years). Majority (76%) were males. The most common morphological variant was placoid OSSN (18, 47%). Limbus was the most common epicenter (31, 82%). Corneal OSSN was the most initially misdiagnosed variant (n = 3). Of the 38 eyes receiving one week on and 3-weeks off cycles of 5FU regimen, complete tumor resolution was achieved in 36 (95%) eyes. The median number of topical 5FU cycles for tumor resolution was 2 (mean, 2; range, 1 to 4). Over a median follow-up period of 5 months (mean, 6 months; range, 1 to 27 months), tumor recurrence was noted in 3 eyes (8%), of which one case had xeroderma pigmentosum with bilateral multifocal recurrence. Complication rate was 5% (n = 2), which included transient conjunctival hyperemia (n = 1), and bacterial keratitis (n = 1) which resolved with fortified antibiotics. CONCLUSION: Primary chemotherapy with topical 1% 5FU is a safe and effective management modality for OSSN at limited resource settings in rural India.

Epidemiology and risk factors for the development of cicatrizing conjunctivitis in chronic ocular graft-versus-host disease.

PURPOSE: To evaluate the incidence of chronic cicatrizing conjunctivitis (CCC) and its associated risk factors in the context of chronic ocular graft-vs-host disease (coGVHD). METHODS: A retrospective chart review of individuals diagnosed with coGVHD following hematopoietic stem cell transplantation (HSCT) who were seen at the Bascom Palmer Eye Institute between May 2010 and November 2021 was performed. Data regarding baseline demographic characteristics, systemic co-morbidities, lid margin abnormalities, ocular cicatricial changes, transplant information, immunosuppressive therapy, and GVHD severity assessments were collected. The incidence of cicatricial conjunctivitis was estimated with Kaplan-Meier survival analysis. A Cox regression model was used to assess the contribution of demographic and systemic variables to the development of CCC. RESULTS: 167 individuals were included (53.9 ± 14.7 years old; 60.5 % male). 65 individuals presented with features suggestive of CCC an average of 60.9 ± 53.8 months after HSCT, with 60-month and 120-month incidences of 29.3 % and 48.9 %, respectively. Multivariable analysis demonstrated that age younger than 50 at the time of the first eye visit was associated with a higher chance of CCC development (Hazard Ratio (HR): 2.14, 95 % Confidence Interval (CI): 1.16-3.97, p = 0.02). CONCLUSION: Clinically detected cicatrizing conjunctivitis is an ocular manifestation of coGVHD, with an incidence that increases over time. Younger individuals may be at higher risk for CCC development.

Comparison of upper eyelid pressure and ocular surface parameters in dry eye disease and benign essential Blepharospasm: A cross-sectional study.

PURPOSE: To compare the upper eyelid pressure (UEP) and ocular surface parameters between dry eye disease (DED) and DED coexisting with benign essential blepharospasm (BEB), exploring which parameters could assist in distinguishing between DED and BEB, as potential risk factors for DED with BEB. METHODS: All enrolled participants diagnosed with DED or DED coexisting with BEB were initially subjected to ocular surface disease index (OSDI) determination. Subsequently, the upper eyelid pressure was recorded using an innovative eyelid pressure measurement device, followed by a series of ocular surface examinations. The two groups were compared using the independent t-test and Mann-Whitney U test. A logistic regression analysis was performed to identify which parameters can predict the onset of blepharospasm. RESULTS: The BEB group achieved a higher upper eyelid pressure (101.9 ± 23.5mN vs 88.4 ± 18.1mN, P = 0.009), lower number of total blink (6.2 ± 4.2 vs 7.1 ± 4.1, P = 0.016), higher corneal fluorescein staining score (4.0 ± 1.9 vs 3.0 ± 1.7, P = 0.046), higher partial blink rate (0.9 ± 0.2 vs 0.5 ± 0.4, P = 0.000) and the lower grade of meibum expressibility (1 (1, 2) vs 2 (1, 3), P = 0.000) and meibum quality (1 (1, 1) vs 1 (1, 1), P = 0.033) compared with the DED group. The upper eyelid pressure (OR = 1.123), partial blink rate (OR = 0.014) and the grade of meibum expressibility (OR = 10.804) showed significant associations with BEB (P < 0.05). CONCLUSION: Despite similar OSDI scores, DED coexisting with BEB exhibited higher upper eyelid pressure, lower corneal fluorescein staining score, lower partial blink rate, more total blinks, lower grades of meibum expressibility, and lower meibum quality compared to DED alone. Among these, higher upper eyelid pressure, lower partial blink rate, and worse grade of meibum expressibility were identified as risk factors for BEB in DED.

Evaluation of ocular surface parameters before and after cryo- and laser therapy for distichiasis in dogs: A pilot study.

OBJECTIVE: The aim of this pilot study was to establish a satisfactory, scientific approach to effectively compare quantitative measurements of various ocular surface parameters before and after surgical treatment in dogs suffering from distichiasis. METHODS: An ophthalmic examination was conducted on 12 dogs (23 eyes) before and after surgical treatments for distichiasis, at four different time points, (t0 = before surgery, t1 = 1-2 h after surgery, t2 = 1 week after surgery, t3 = 1 month after surgery, and t4 = 6 months after surgery) between 2021 and 2022, and analyzed retrospectively. The examination included Schirmer tear test-1 (STT-1), interferometry, noninvasive tear film break-up time (NIBUT), tear meniscus size (TMS), and meibography. RESULTS: No statistically significant changes were found in STT-1 (t0: 22.2 ± 6.5 mm, t2: 22.5 ± 5.7 mm, t3: 20.8 ± 5.1 mm, and t4: 22.6 mm ± 4.8 mm) before and after surgery. Mean interferometry scores showed a slight, not statistically significant, decrease from t0 to t3 and t4 (t0: 2.1 ± 0.8, t1: 2.1 ± 0.7, t2: 2.1 ± 0.9, t3: 1.8 ± 0.6, and t4: 1.9 ± 1.1). Mean NIBUT did not change significantly between time points (t0: 3.9 ± 1.3 s, t1: 4.0 ± 1.3 s, t2: 4.0 ± 1.4 s, t3: 3.5 ± 0.7 s, and t4: 3.5 ± 0.9 s). TMS showed a slight, not statistically significant increase (t0: 0.5 ± 0.3 mm, t1: 0.5 ± 0.3, t2: 0.5 ± 0.3 mm, t3: 0.6 ± 0.2 mm, and t4: 0.7 ± 0.3 mm). There were no changes in the gross morphology of the meibomian glands (MG). CONCLUSION: This pilot study could not detect a negative effect of different forms of treatment of distichiasis on the precorneal tear film parameters in dogs. However, due to the study's retrospective nature and small sample size, no definitive conclusion can be drawn regarding the changes at the different time points.

Corneal and Ocular Surface Contributions From Mexico: A Bibliometric Analysis From 1913 to 2022.

OBJECTIVE: This study aimed to investigate all recorded corneal and ocular surface research by Mexican authors. METHODS: The output data was extracted from SCOPUS to account for all publications regarding the corneal or ocular surface by Mexican authors. Data screening, extraction, and critical revision were performed by two of the authors to avoid duplication and ensure the authenticity of all papers. Performance analysis, science mapping, and network metrics were employed to retrieve trends in publication. RESULTS: A total of 1,091 indexed journal documents by 3965 authors were retrieved, covering the period the period from 1919 to 2022. In performance analysis, the document types included 881 articles, 20 book chapters, 17 conference papers, three editorials, 37 letters to the editor, nine notes, and 123 reviews. A total of 3,965 contributing authors made 6,081 author appearances. In terms of total citations per country, Mexican authors received a total of 7,087 citations, with an average article citation of 8.76 per author. CONCLUSION: This bibliometric analysis highlights impactful research contributions to corneal and ocular surface research from Mexican authors, identifies influential authors and institutions, and also emphasizes the need for increased interaction in the international arena.

Ocular Surface Squamous Neoplasia in Renal Transplant Patients.

Transplantation surgery becomes more widespread with time worldwide; organ transplantation increases the risk of developing malignancies. This phenomenon is primarily due to immunosuppressive treatment which is one of the mainstay approaches to prevent transplant rejection. It is aimed to describe clinical signs and symptoms of histologically proven ocular surface squamous neoplasia (OSSN) in renal transplant patients. Three patients, who previously underwent renal transplant surgery, diagnosed with OSSN are presented. The histopathological examination results were conclusive for squamous cell neoplasia in all cases. No recurrence in any patients was observed after total surgical excision, cryotherapy, and reconstruction with amniotic membrane. Solid organ transplant patients undergo intense immunosuppressive treatment to prevent transplant rejection. That immunosuppressive treatment increases the risk of developing secondary malignancies including OSSN. It is important to inform all transplant patients about these risks. Even though OSSN is known to be a relatively benign acting tumor that rarely metastasizes to distant organs, the clinical course might change if it develops in an immunocompromised patient. For this reason, these patients should be monitored for any formation of a mass on the ocular surface. Surgical management through complete excision can result in the complete resolution of a tumor.

A machine learning approach to predicting dry eye-related signs, symptoms and diagnoses from meibography images.

Purpose: To use artificial intelligence to identify relationships between morphological characteristics of the Meibomian glands (MGs), subject factors, clinical outcomes, and subjective symptoms of dry eye. Methods: A total of 562 infrared meibography images were collected from 363 subjects (170 contact lens wearers, 193 non-wearers). Subjects were 67.2 % female and were 54.8 % Caucasian. Subjects were 18 years of age or older. A deep learning model was trained to take meibography as input, segment the individual MG in the images, and learn their detailed morphological features. Morphological characteristics were then combined with clinical and symptom data in prediction models of MG function, tear film stability, ocular surface health, and subjective discomfort and dryness. The models were analyzed to identify the most heavily weighted features used by the algorithm for predictions. Results: MG morphological characteristics were heavily weighted predictors for eyelid notching and vascularization, MG expressate quality and quantity, tear film stability, corneal staining, and comfort and dryness ratings, with accuracies ranging from 65 % to 99 %. Number of visible MG, along with other clinical parameters, were able to predict MG dysfunction, aqueous deficiency and blepharitis with accuracies ranging from 74 % to 85 %. Conclusions: Machine learning-derived MG morphological characteristics were found to be important in predicting multiple signs, symptoms, and diagnoses related to MG dysfunction and dry eye. This deep learning method illustrates the rich clinical information that detailed morphological analysis of the MGs can provide, and shows promise in advancing our understanding of the role of MG morphology in ocular surface health.

Comparison of two digital alignment systems for toric intraocular lens implantation.

PURPOSE: To compare the two most used digital alignment systems regarding precision, repeatability and loss of track. METHODS: 15 eyes of 15 patients older than 21 years with cataracts were included in this prospective study. The two systems were intraoperatively superimposed and recorded, and the alignment of the two displayed alignment axes was analysed regarding precision, repeatability and loss of track. RESULTS: There was a significant difference in precision and repeatability between the two digital alignment systems regarding the projected alignment axis. The deviation from the actual target axis was significantly different, with a mean of 0.34°±0.75° for the Zeiss system and 1.60°±1.08° for the Alcon system (p=0.03, n=14). The within-subject SD was significantly lower with 0.21° for the Zeiss system and 0.34° for the Alcon system (p=0.03, n=14). CONCLUSIONS: The Zeiss Callisto system showed a significantly lower deviation from the target axis, higher stability with eye movements and less need for microscope illumination than the Alcon system. Both systems showed high precision when compared with manual marking methods. TRIAL REGISTRATION NUMBER: NCT05220683.

Investigation of eye flora in cats infected with Herpesvirus and Calicivirus.

Background and Objectives: The ocular surface is perpetually exposed to the external environment, rendering it susceptible to microbial contamination. The ocular surface microbiota consists of non-pathogenic microorganisms that inhabit the conjunctiva and cornea. This study's objective was to extensively review the prevalence of bacterial and fungal organisms in the conjunctiva of healthy and diseased cats. (Herpes- and Calici-infected groups). Materials and Methods: The current study was performed on 240 cats that had visited veterinary health centers (Tehran, Iran) for examination. Sterile swabs from each cat's eyes were investigated for microbiological assessment. After sample collection, viral pathogens (Herpes and Calici viruses) were isolated and identified using the PCR method. The ages of the investigated group were 3.76, 3.93, and 4.15 months. Results: The highest frequency of bacteria in the normal, Herpes-infected/Calici-infected, and Herpes/Calici-infected groups were associated with Staphylococcus intermedius and Streptococcus agalactiae, Staphylococcus epidermidis, and Staphylococcus intermedius, respectively. In addition, it was found that the high prevalence of fungal microorganisms in the isolated samples was related to yeasts, Aspergillus (Aspergillus fumigatus, Aspergillus niger), and Penicillium species. Conclusion: Bacterial prevalence was significantly higher in all groups than the prevalence of fungi in the eyes of cats. The statistical comparison between the study groups regarding microbial and fungal frequency showed that significant differences were found between them, such that the frequency was higher in all disease groups, against the control group. In addition, a significant relation was observed between the Herpes-infected and Calici-infected groups regarding microbial and fungal prevalence.

Silk-Derived Protein-4 versus vehicle control in treating patients with moderate to severe dry eye disease: a randomized clinical trial.

PURPOSE: In this study the safety and efficacy of silk-derived protein 4 (SDP-4), also known as amlisimod, eye drops against a vehicle control formulation in patients with moderate to severe dry eye disease (DED) was assessed. SDP-4 is a novel, naturally derived, anti-inflammatory wetting agent that enhances coating on the ocular surface. DESIGN: Exploratory Phase 2, 12- and 8-week, serial cohort, multicenter, double-masked, randomized, vehicle-controlled study. METHODS: In the first cohort (N=305), patients were randomized 1:1:1:1 to SDP-4 (0.1%, 1%, 3% wt./wt.) or vehicle control and dosed two times per day (BID), while in the second cohort patients were randomized 1:1 with 1% wt./wt. SDP-4, the best performing formulation from the first cohort, or vehicle control BID (N=151). Diagnosed DED patients were treated in the United States between April 2019 and May 2021. The first cohort of subjects had moderate to severe baseline symptoms, while the second cohort had moderate baseline symptoms to study the impact of baseline symptoms on SDP-4 performance. Key sign and symptom end points were mean change from baseline in TBUT and total SANDE score (0-100 visual analog scale) throughout the study. RESULTS: SDP-4 (1%) significantly increased TBUT vs the vehicle control (P<0.05) at days 28 and 56 in the first cohort, and patient symptomatology from baseline was reduced by 46% based on subject reported SANDE VAS scores at day 84. Patients with more severe baseline DED symptoms experienced a significantly greater amount of relief than when compared to patients with moderate DED (P<0.05). All treatment groups were well tolerated with a 2.6% total discontinuation rate. CONCLUSIONS: To the best of our knowledge, this was the first-in-human use of SDP-4 in a clinical trial. SDP-4 is a first-in-class protein ingredient that offers a safe and multi-modal treatment approach for alleviating severe DED symptoms within a novel formulation.

The relationship between sex hormone levels and ocular surface parameters in girls with idiopathic central precocious puberty.

Purpose: The study aimed to investigate the correlation between the change of sex hormone levels and ocular surface parameters in girls with idiopathic central precocious puberty(ICPP). Methods: Eighteen girls with ICPP and 18 age-matched normal girls participated in this study, all of the participants had undergone physical measurements, laboratory tests, imaging examination and ocular surface assessments. Results: The Objective Scatter Index (OSI) in the ICPP group was significantly higher than in the control group (P = 0.031), girls with ICPP showed slightly lower MNITBUT compared to the normal control group, although this difference was not statistically significant. Bivariate analysis revealed a positive association between estradiol and OSI (r=0.383, P=0.021), Additionally, in the study population, both Luteinizing hormone (LH) and Follicle-stimulating hormone (FSH) were negatively correlated with Mean noninvasive tear breakup time (MNITBUT) (r=-0.359, P=0.031)(r=-0.357, P=0.032). Conclusion: In comparison with the normal control group, alterations in the OSI were observed in girls with ICPP. This alteration may be associated with an elevation in estrogen levels. Although there was a slight non-significant decrease in NITBUT in ICPP girls, the negative correlation between LH and FSH with MNITBUT suggests new perspective for further investigation.

Atypical presentation of a lymphangioma as a conjunctival horn.

Conjunctival lymphangiomas are rare hamartomas of lymphatic origin that are usually located in the bulbar conjunctiva. They commonly present either as focal or diffuse bulbar chemosis or as dilatation of lymphatic vessels that resembles an isolated cyst or a group of cysts. There can be bleeding inside the lymphangioma resulting in "chocolate cysts".1 We report the unusual case of a conjunctival lymphangioma on a 36 year-old male that presented as a large horn-like protruding structure. The lesion was surgically removed with simple excision associated with cryotherapy to the lesion's borders, as malignancy could not be ruled out preoperatively. Histopathological examination revealed a lymphangioma composed of an ill-defined proliferation of dilated lymphatic channels in the lamina propria, underlying conjunctival epithelium with squamous metaplasia, acanthosis and hyperkeratosis. One year postoperatively, the patient remains asymptomatic and without recurrence of the lesion.