Ocular Surface Environment Research Articles

A Case of Corneal Ulcer Caused by Stenotrophomonas maltophilia in a Healthy Patient

Purpose: To report a case of corneal ulcer caused by <i>Stenotrophomonas maltophilia</i> monomicrobial infection in an otherwise healthy patient, devoid of underlying medical conditions or predisposing factors.Case summary: A 48-year-old male patient, who was normally healthy without a history of systemic disease, eye trauma, and eye surgery, presented with acute left eye pain that had manifested one day prior. Ophthalmic examination revealed conjunctival injection, corneal edema, and localized corneal ulceration in the left eye. Suspecting infectious keratitis, diagnostic procedures including gram staining, bacterial and fungal cultures, and antibiotic susceptibility testing were promptly instituted. Bacterial culture identified <i>S. maltophilia</i>, prompting an eight-week course of topical gatifloxacin therapy. The subsequent clinical course exhibited improvement, with lingering corneal haziness and the restoration of visual acuity to 1.0.Conclusion: The case featuring the single detection of <i>S. maltophilia</i>, known to cause hospital-acquired opportunistic infections, emphasizes the importance of culture and antibiotic susceptibility testing in the treatment of keratitis. Remarkably, in a patient with a normal immune status and in the absence of factors predisposing to <i>S. maltophilia</i> infections, there were no discernible causative factors damaging the ocular surface environment.

A Rat Dry Eye Model with Lacrimal Gland Dysfunction Induced by Scopolamine.

Aqueous-deficient dry eye (ADDE) is a type of dry eye disease that can result in the reduction of tear secretion quantity and quality. Prolonged abnormal tear production can lead to a disturbance in the ocular surface environment, including corneal damage and inflammation. In severe cases, ADDE can cause vision loss or even blindness. Currently, dry eye treatment is limited to eye drops or physical therapy, which can only alleviate eye discomfort symptoms and cannot fundamentally cure dry eye syndrome. To restore the function of the lacrimal gland in dry eye, we have created an animal model of lacrimal gland dysfunction in rats induced by scopolamine. Through the comprehensive evaluation of the lacrimal gland, corneas, conjunctivas, and other factors, we aim to provide a full understanding of the pathological changes of ADDE. Compared with the current dry eye mouse model, this ADDE animal model includes a functional evaluation of the lacrimal gland, providing a better platform for studying lacrimal gland dysfunction in ADDE.

Use of a Cationic Emulsion of Latanoprost to Treat Glaucoma Patients with Ocular Surface Disease: A Preclinical Review.

Prostaglandin analogue topical medications are one of the most effective therapeutic approaches for the chronic management of glaucoma and ocular hypertension, through the reduction of elevated intra ocular pressure (IOP). While many of the first generations of anti-glaucoma eye drops were preserved with benzalkonium chloride, their repeated use may induce chronic ocular surface toxicity that leads to ocular surface disease (OSD) signs and symptoms. As a result, soft-preservatives and preservative-free formulations have been developed with the goal to avoid the long-term iatrogenic toxicity of the preservative agents. In addition, it has been suggested that OSD and its associated inflammation may negatively impact the efficacy of the IOP-lowering medications, including treatment adherence and compliance. Hence, it may be particularly interesting that glaucoma medications can concomitantly protect and "heal" the ocular surface and its environment while lowering elevated IOP, for the greater benefit of glaucoma patients. The objective of the present review is to briefly present the preclinical data of the cationic oil-in-water emulsion of latanoprost (latanoprost-CE) to shed some light on its mechanisms of action. It overall supports the following hypothesis: the restoration of a healthy ocular surface environment and treatment of the OSD signs and symptoms will allow for an improved elevated IOP reduction and glaucoma management. This would be achieved with a once daily dosing regimen to preserve glaucoma patients' vision, ocular surface, and quality-of-life and wellness.

Association between Air Pollution Exposure and Daily Outpatient Visits for Dry Eye Disease: A Time-Series Study in Urumqi, China

The potential effects of air pollution on the ocular surface environment have not been fully evaluated, and even fewer studies have been conducted on the lagged effects of air pollution on dry eye disease (DED). The data of 9970 DED outpatients between 1 January 2013 and 31 December 2020, and data for six air pollutants, including PM10, PM2.5, carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3), were obtained from 11 standard urban background stationary air quality monitors in Urumqi, Xinjiang, China. Time series analysis design and quasi-Poisson generalized linear regression models combined with distributed lagged nonlinear models (DLNM) were used. Single- and multi-pollutant model results suggest that each additional per 10 μg/m3 of PM10, NO2, and SO2 is associated with an increased risk of outpatient DED on lag day 0 and PM2.5, NO2, and SO2 with other cumulative lag days; R software version 4.0.4 (15 February 2021) was used for the analysis. We conducted first time series analysis with a large sample size in northwest China (Xinjiang) and confirmed, for the first time, the impact of air pollution including particulate pollutants (PM10, PM2.5) and acidic gasses (SO2, NO2) on DED risk in the Urumqi region, and suggested the potential lagged effects of PM2.5, SO2, and NO2.

Stem cells versus keratoprostheses

AbstractRoutine penetrating keratoplasty will not survive well in some circumstances, including harsh ocular surface environment, stem cell deficiency and chronic ocular inflammation. Fortunately, there have been advances to restore vision in these conditions in two directions: artificial keratoplasty and limbal stem cell transplantation. The recipient eye should have an intact lid mechanism and good tear film for stem cell transplantations. There may also be a need for future lamellar or penetrating keratoplasty with a chance for graft rejection. Treatment of unilateral limbal stem cell deficiency is relatively simple with three surgical options: Conjunctival Limbal Autograft (CLAU), Cultivated Limbal Epithelial Transplantation (CLET) and Simple Limbal Epithelial Transplantation (SLET). However, most patients have bilateral diseases like Stevens‐Johnson syndrome (SJS), aniridia and mucous membrane pemphigoid (MMP). In this scenario, an allogenic source for limbal stem cells is needed.Moreover, systemic immunosuppressive will be required to decrease the chance of rejection. Another option is Cultured Oral Mucosal Epithelial Transplantation (COMET) which usually provides less optimal visual acuity. The last option is keratoprosthesis (KPro). Many KPro devices have come and gone through, and two clear winners have emerged: Boston Keratoprosthesis KPro type I Osteo‐odonto‐keratoprosthesis, also known as the ‘OOKP’ OOKP is suitable for patients with severe dry eye and permanent lid damage. These patients should be excluded from any type of stem cell transplantation due to the inevitable chance of failure. However, Boston KPro type I may be considered as an alternative option for stem cell transplantation. Recent meta‐analysis for comparison of Keratolimbal Allograft (KLAL) and Boston KPro I in eyes affected by chemical burn has shown quite similar outcomes. Though, it should be mentioned that there are many limitations in included studies that make it difficult to reach an accurate conclusion. KPro has the advantages of shorter rehabilitation time and no need for systemic immunosuppression.Nevertheless, there is more chance of complications or loss of visual potential with KPro. Corneal surgeons should, in fact, be familiar with both options of KPro and stem cell transplantation to guide their patients towards the correct choice of treatment. The learning curve of such surgical techniques is steep. An extended follow‐up time is necessary to evaluate the safety of any method.

Effect of Transcutaneous Upper Eyelid Blepharoplasty on Blink Parameters and Lipid Layer Thickness.

Purpose: This study aimed to investigate the effect of transcutaneous upper eyelid blepharoplasty on lipid layer thickness (LLT) and blink parameters in young women during the early postoperative period.Methods: This prospective study included 110 eyes of 55 young female patients (age range, 19–31 years) who underwent transcutaneous upper eyelid blepharoplasty. The LLT and blink parameters measured using a LipiView interferometer were recorded before the surgery and 1 week and 1 month after the surgery. Ocular Surface Disease Index (OSDI) score, noninvasive tear film breakup time (NITBUT), and palpebral fissure height (PFH) measurements were also performed at each time point.Results: The number of blinks significantly decreased (P < 0.001), and the number of partial blinks and partial blink rate (PBR) significantly increased 1 week after the surgery (P = 0.002 and P < 0.001); they all returned to baseline in 1 month. The LLT and OSDI score increased significantly 1 week and 1 month after the surgery (P < 0.001 and P < 0.001). A significant increase in the NITBUT and a significant decrease in the PFH were observed 1 week after the surgery (P < 0.001 and P < 0.001), and the values returned to baseline 1 month after the surgery. No clinical correlation was found between blink parameters and ocular surface parameters.Conclusions: Transcutaneous upper eyelid blepharoplasty led to a change in blink parameters and ocular surface parameters during the early postoperative period. However, this influence was temporary, and the transitory change in blink parameters had no effects on the ocular surface environment.

Using Buccal Mucosa and Auricular Cartilage With a Local Flap for Full-Thickness Defect of Lower Eyelid.

Reconstruction of full-thickness eyelid wounds is challenging. In this case, using buccal mucosa to repair the conjunctival surface of the lower eyelid defect maintain the function of the conjunctival surface, reduce the damage to the original ocular surface environment. Using autologous auricular cartilage as the skeleton of the eyelid defect, provided better support for the flap, and the site had a good esthetic appearance after surgery. Using skin flap to repair the skin surface of the lower eyelid defect, the eyelid defect can be repaired and good clinical results can be obtained.

Modify and protect ocular surface environment during dry eye disease: the role of a harmonic system in the evolution of replacement therapy for tear dysfunctions

Modify and protect ocular surface environment during dry eye disease: the role of a harmonic system in the evolution of replacement therapy for tear dysfunctions

Dorsolateral medullary infarction registry: a study protocol for a prospective, multicentric registry

BackgroundDorsolateral medullary infarction is a typical cerebral infarction which is characterized by Wallenberg’s syndrome. Neurotrophic keratopathy is an uncommon consequence of dorsolateral medullary infarction. At present, the protocol is aimed to study the dynamic changes in corneal innervation and the ocular surface environment after dorsolateral medullary infarction.MethodsThis study will involve consecutive data from all medical records of patients within 7 days of acute dorsolateral medullary infarction onset at the Departments of Neurology from 10 collaborating stroke centers. Eligible patients will mainly be characterized based on detailed physical examinations, multimodal imaging, and corneal related examinations and patients will be followed-up for 2 years. Neurotrophic keratopathy after dorsolateral medullary infarction is the primary endpoint. The dynamic histological corneal innervation and ocular surface environment after dorsolateral medullary infarction will be observed during the follow-up period.DiscussionThis multicentric, prospective registry is the first to identify and characterize the dynamic changes of corneal innervation and the ocular surface environment after acute dorsolateral medullary infarction. The significance of the study is to emphasize that the curative effect is based on the doctors’ identification of the disease in the earliest stage before irreversible damage occurs to the cornea. Trial registrationThe registry was registered (ChiCTR-OPC-17,011,625) on June 11, 2017.

Minor salivary gland transplantation for severe dry eye disease due to cicatrising conjunctivitis: multicentre long-term outcomes of a modified technique

AimTo report the clinical outcomes of autologous minor salivary gland transplantation (MSGT) for the treatment of severe dry eye disease caused by cicatrising conjunctivitis.MethodsThis was a retrospective case series of...

Emerging Approaches for Ocular Surface Regeneration.

In this manuscript, the recent advancements and novel approaches for regeneration of the ocular surface are summarized. Following severe injuries, persistent inflammation can alter the rehabilitative capability of the ocular surface environment. Limbal stem cell deficiency (LSCD) is one of the most characterized ocular surface disorders mediated by deficiency and/or dysfunction of the limbal epithelial stem cells (LESCs) located in the limbal niche. Currently, the most advanced approach for revitalizing the ocular surface and limbal niche is based on transplantation of limbal tissues harboring LESCs. Emerging approaches have focused on restoring the ocular surface microenvironment using (1) cell-based therapies including cells with capabilities to support the LESCs and modulate the inflammation, e.g., mesenchymal stem cells (MSCs), (2) bio-active extracellular matrices from decellularized tissues, and/or purified/synthetic molecules to regenerate the microenvironment structure, and (3) soluble cytokine/growth factor cocktails to revive the signaling pathways. Ocular surface/limbal environment revitalization provide promising approaches for regeneration of the ocular surface.

Cataract surgery in ocular surface diseases: clinical challenges and outcomes.

Cataracts are a significant cause of blindness and visual impairment worldwide. With the recent advances in cataract surgery techniques, outcomes have improved significantly in uncomplicated cases. This article discusses the challenges and outcomes of cataract surgery in complex cases targeting eyes with ocular surface diseases like Stevens-Johnson syndrome, ocular cicatricial pemphigoid, Mooren's ulcer, vernal keratoconjunctivitis and limbal stem cell deficiency. Ocular surface diseases are commonly associated with corneal scarring and vascularization, conjunctival inflammation, symblepharon and forniceal shortening. Any surgical intervention in a hostile ocular surface environment may worsen the disease, which may result in visual deterioration. In recent past, with the use of immunosuppressants and with the introduction of different ocular surface reconstruction surgeries; stabilization of ocular surface can be achieved prior to planning cataract surgery. This kind of step-wise approach can considerably improve visual outcomes in such cases. Cataract surgery in ocular surface diseases needs careful preoperative, intraoperative and postoperative planning. Performed in a staged manner under favorable ocular environment, it has good visual outcomes and can improve the quality of life in such patients.

Meibomian Gland Dysfunction Correlates to the Tear Film Instability and Ocular Discomfort in Patients with Pterygium

Pterygium is a very common disease in an eye clinic characterized by a benign proliferation of local conjunctiva that often crosses the limber of cornea and extends into corneal surface. Variety of studies has showed that pterygium is able to result in ocular discomfort and the change of ocular surface environment, such as dry eye. However, the link between abnormal tear film function and pterygium is controversial. Meibomian gland dysfunction (MGD) is a common cause of dry eye and ocular discomfort but is often neglected, which may be the missing link between dry eye and pterygium. In this study, our data firstly revealed increased abnormality of meibomian gland structure and function in pterygium patients, representing with increased abnormality of MGD parameters such as meibum expression (P < 0.001) and meibomian gland loss (P < 0.001). Besides, the scores of MGD severity in patients with progressive pterygium were higher than those in patients with resting pterygium. The correlation between MGD parameters and ocular discomfort as well as dry eye indexes is also established. These findings suggest that MGD correlates to the tear film instability and ocular discomfort in patients with pterygium.

End-of-day dryness, corneal sensitivity and blink rate in contact lens wearers.

To study the relationship among the variables intensity of the end-of-day (EOD) dryness, corneal sensitivity and blink rate in soft contact lens (CL) wearers. Thirty-eight soft CL wearers (25 women and 13 men; mean age 27.1±7.2 years) were enrolled. EOD dryness was assessed using a scale of 0-5 (0, none to 5, very intense). Mechanical and thermal (heat and cold) sensitivity were measured using a Belmonte's gas esthesiometer. The blink rate was recorded using a video camera while subjects were wearing a hydrogel CL and watching a film for 90 min in a controlled environmental chamber. A significant inverse correlation was found between EOD dryness and mechanical sensitivity (r: -0.39; p=0.02); however, there were no significant correlations between EOD dryness and thermal sensitivity. A significant (r: 0.56; p<0.001) correlation also was observed between EOD dryness and blink rate, but no correlations were found between blink rate and mechanical or thermal sensitivity. CL wearers with higher corneal sensitivity to mechanical stimulation reported more EOD dryness with habitual CL wear. Moreover, subjects reporting more EOD dryness had an increased blink rates during wear of a standard CL type. The increased blink rate could act to improve the ocular surface environment and relieve symptoms.

Immunological Rejection Following Allogeneic Cultivated Limbal Epithelial Transplantation

A llogeneic cultivated limbal epithelial transplantation (CLET), including living-related CLET, is recommended for bilateral cases with limbal stem cell deficiency or for unilateral cases in which the patient wishes to preserve the limbal function of the healthy fellow eye. For a long-term successful corneal epithelial restoration, it is important to maintain a suitable ocular surface environment and to prevent allograft rejection. Previous reports1-3 on allogeneic CLET have indicated only the incidence of allograft rejection, with no information on the clinical course or on anterior segment findings.Wepreviouslyexamined13patientswho underwent allogeneic CLETwithout any episodes of allograft rejection.2 The details of the epithelial sheet preparation and CLET procedures have also been outlined previously.4 Thereafter, we performed 37 allogeneic CLET procedures in 31 eyes and experienced 3 rejection episodes in 2 eyeswith characteristic clinical manifestations. Herein, we describe 2 cases who developed clinically significant allograft rejection reactions.

Determination of Tear and Serum Inflammatory Cytokines in Patients with Rosacea Using Multiplex Bead Technology

Purpose: To compare serum and tear inflammatory and anti-inflammatory cytokine levels of rosacea patients with the healthy controls and evaluate the correlation of tear cytokine levels with tear function parameters.Methods: Tear and serum interleukin (IL)-1α, IL-6, IL-8, IL-10, monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), epidermal growth factor (EGF), and vascular endothelial growth factor (VEGF) levels were measured using multiplex bead (Luminex) technology in 12 rosacea patients without ocular involvement (group 1), 20 rosacea patients with ocular involvement (group 2), and 22 healthy subjects (group 3). The correlation of the cytokines with tear function parameters was analyzed using Spearman correlation test.Results: Tear IL-10 and VEGF levels were significantly lower in group 1 (median: 35.78 pg/mL and 427.29, respectively) and group 2 (median: 26.25 pg/mL and 348.31, respectively) than in group 3 (median: 75.96 pg/mL and 480.12, respectively) (p < 0.05). Mean serum IL-8 level was significantly lower in group 2 (median = 0) compared to group 3 (median = 3.98) (p = 0.02). Tear breakup time was found to be positively correlated with IL-10 (r = 0.46, p = 0.013) and inversely correlated with MCP-1 (r = −0.52, p = 0.004).Conclusions: Tear and serum levels of cytokines and growth factors measured with Luminex technology showed a large variation in rosacea and healthy subjects. Decreased levels of tear IL-10, an anti-inflammatory cytokine, may lead to an inflammatory ocular surface environment, exacerbate ocular surface inflammation, and deteriorate tear function tests. A bigger sample size, including rosacea patients with corneal involvement, is needed to confirm the role of cytokines in the pathogenesis of rosacea-associated ocular inflammation.

Comparison of the anti‐inflammatory effects of artificial tears in a rat model of corneal scraping

AbstractPurpose The aim of the present study was to evaluate the safety and tolerance of cationic oil‐in‐water emulsion on debrided cornea, and to characterize its benefits on the corneal epithelium healing process.Methods A rat model of corneal scraping was used to characterize the effects of four commercially available artificial tears (Cationorm®, Vismed®, Optive® and Systane Balance®) on the recovery process of the debrided corneas. The upper part of the corneal epithelium was scraped mechanically prior to a 5‐day treatment with different artificial tears. At the end of the treatment, the ocular surface was evaluated clinically (corneal fluorescein staining, CFS) and by in vivo confocal microscopy (IVCM). Conjunctival function was assessed by goblet cell count and MUC5AC immunostaining.Results The four artificial tears were all well tolerated by the debrided cornea. By restoring an adequately hydrated ocular surface environment they promote corneal healing, as evidenced by CFS measurements of the scraped area. In contrast 0.02% BAK solution inhibits the healing process. IVCM analysis of the different layers of the cornea confirmed the benefits of the cationic emulsion (Cationorm®). Interestingly inflammatory cells infiltration in the stroma was at its lower following Cationorm® treatment, while 0.02% BAK treatment resulted in marked inflammation. The different treatments were all able to protect goblet cells function and MUC5AC expression.Conclusion BAK‐free cationic emulsion (Cationorm®) is well tolerated by debrided cornea and allow for a safe healing of the cornea. The findings suggest that Cationorm® have the potential to benefit patients with corneal epithelium disorder. Commercial interest

Surgical management of lacrimal punctal cauterization in chronic GVHD-related dry eye with recurrent punctal plug extrusion

We investigated the efficacy of lacrimal punctal occlusion surgery with a cautery device in patients with chronic GVHD (cGVHD)-related dry eye, with recanalization of puncta and recurrent punctal plug extrusion. A total of 23 puncta from 14 eyes of 10 patients with chronic GVHD (cGVHD)-related dry eye underwent punctual thermal cauterization with a high-temperature disposable cautery device. All patients were refractory to conventional treatment, including artificial tear eye drops, autologous serum eye drops and vitamin A eye drops, and had a history of recanalization and recurrent punctal plug extrusion. The effect of lacrimal punctal cauterization by thermal cautery device was evaluated by changes in subjective symptom scores, corrected distance visual acuity, Schirmer's test values, fluorescein staining scores, rose bengal staining scores, and tear-film break-up time before and 3 months after the surgery. Subjective symptom scores, Schirmer's test values, fluorescein and rose bengal scores, and tear-film break-up time improved significantly 3 months after the surgery. Recanalization of puncta was not observed in all the cases (0 of 14 eyes, 0%). Lacrimal punctal cauterization was effective with no recanalization and significant improvements in subjective symptoms and the ocular surface environment in cGVHD-related dry eye patients who had been refractory to conventional treatments.

Ocular surface immunity: Homeostatic mechanisms and their disruption in dry eye disease

The tear film, lacrimal glands, corneal and conjunctival epithelia and Meibomian glands work together as a lacrimal functional unit (LFU) to preserve the integrity and function of the ocular surface. The integrity of this unit is necessary for the health and normal function of the eye and visual system. Nervous connections and systemic hormones are well known factors that maintain the homeostasis of the ocular surface. They control the response to internal and external stimuli. Our and others' studies show that immunological mechanisms also play a pivotal role in regulating the ocular surface environment. Our studies demonstrate how anti-inflammatory factors such as the expression of vascular endothelial growth factor receptor-3 (VEGFR-3) in corneal cells, immature corneal resident antigen-presenting cells, and regulatory T cells play an active role in protecting the ocular surface. Dry eye disease (DED) affects millions of people worldwide and negatively influences the quality of life for patients. In its most severe forms, DED may lead to blindness. The etiology and pathogenesis of DED remain largely unclear. Nonetheless, in this review we summarize the role of the disruption of afferent and efferent immunoregulatory mechanisms that are responsible for the chronicity of the disease, its symptoms, and its clinical signs. We illustrate current anti-inflammatory treatments for DED and propose that prevention of the disruption of immunoregulatory mechanisms may represent a promising therapeutic strategy towards controlling ocular surface inflammation.

Surgical rehabilitation following severe ocular burns

Chemical and thermal burns can cause devastating injuries to the anterior segment. The consequences of alkali injuries are notoriously severe due to the rapid penetration of these agents into the ocular tissues. Denaturation of tissue, inflammation, and scarring leads to loss of function. An understanding of the pathogenesis of tissue damage has lead to a rational approach to treatment. Emergency irrigation of the eye is essential and there is a 'window of opportunity' during the first 7-10 days after injury when medical treatment can significantly limit the potentially blinding consequences. The acute injury is followed by early and late reparative phases during which the prognosis can be further improved by surgical intervention. Early surgical intervention is targeted at protecting the ocular surface and encouraging re-epithelisation. Later, surgical treatments are directed at ocular surface reconstruction and restoration of vision. However, before any attempt is made at surface reconstruction, the ocular surface environment must be optimised by division of symblepharon, and correction of lid deformity and trichiasis. If there is conjunctivalisation of the corneal surface, limbal stem cell transplantation can restore a corneal epithelial cell phenotype, and transplantation of in vitroamplified corneal epithelial stem cells has been developed as an alternative to keratolimbal transfer techniques. Keratoplasty and cataract surgery may then be necessary to clear the visual axis. Finally, keratoprosthesis is an option for the most severely damaged eyes.