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[Application of impression cytology in diagnosis of ocular surface diseases]

OBJECTIVE: To evaluate the usefulness of impression cytology in diagnosing of ocular surface diseases. METHODS: Impression cytology was performed on 18 eyes with Sjgren's syndrome (dacryosialo-adenopathia atrophicans), 23 eyes with non-Sjgren's syndrome, 15 eyes after thermal or chemical burn at the scarred stage and 20 normal eyes. Conjunctival goblet cell density, conjunctival epithelial squamous metaplasia and corneal cytological features were evaluated respectively. RESULTS: In impression cytology, eyes of Sjgren's syndrome demonstrated a significantly higher grade of squamous metaplasia and lower goblet cell density (P<0.05) as compared with normal eyes and with eyes of non-Sj gren's syndrome in the bulbar conjunctiva, whereas no statistically significant difference of squamous metaplasia grade or goblet cell density was found in the palpebral conjunctiva (P>0.05) in these two groups. In thermal or chemical burned eyes at the scarred stage, the inferior, nasal and temporal bulbar conjunctiva showed higher conjunctival goblet cell density than in the normal eyes (P<0.01). Before surgery of ocular surface reconstruction, conjunctival goblet cells were detected on the corneal area in the 8 thermal or chemical burned eyes. However, the goblet cells in the corneal area of 7 burned eyes were completely resolved after successful ocular surface reconstruction. CONCLUSION The demonstrations of impression cytology in Sjgren's syndrome, thermal or chemical burn are distinctive. Impression cytology is a noninvasive,quick,easy and inexpensive technique, being a useful tool for diagnosis of ocular surface diseases.

Journal Article↗

Amplifying factors in ocular surface diseases: apoptosis.

Apoptosis is a major cell death mechanism that occurs widely in normal tissues and is overstimulated in ocular surface diseases. Apoptosis has been studied specifically in regard to refractive surgery, contact lens wear, and dry eye syndrome. It appears to be closely related to inflammation, as many inflammatory cytokines may promote both inflammation and apoptosis, and their receptors trigger both pathways. A major mediator would play a key role in ocular surface diseases, both at the pro-apoptotic and pro-inflammatory levels, e.g., tumor necrosis factor alpha. This cytokine and its main receptors are, therefore, overexpressed in ocular surface diseases, which makes it a possible target for future therapeutic approaches.

Journal Article↗

Influence of the eye-associated lymphoid tissue (EALT) on inflammatory ocular surface disease.

Certain similarities exist in the pathophysiological processes and clinical features of advanced stages of various inflammatory ocular surface diseases, suggesting that common pathways contribute to these diseases. In this article, common pathways are analyzed with a focus on the role of the physiological resident mucosal immune system of the ocular surface, termed eye-associated lymphoid tissue (EALT). This is physiologically protective but if it is deregulated it can mediate an inflammatory immune answer. Common events in inflammatory ocular surface disease lead to a vicious circle of immune-modulated inflammation, with degenerative remodeling and loss of function.

Journal Article↗

Costs and gains of complex procedures to rehabilitate end stage ocular surface disease.

BACKGROUND: The management of patients with end stage ocular surface disease sometimes requires extensive surgical treatment that can only be provided by specialised ophthalmology. The authors discuss the costs and gains of such complex techniques based on a case of bilateral corneal blindness secondary to Stevens-Johnson syndrome. METHODS AND RESULTS: Despite multiple lid surgery for trichiasis and repeated corneal grafting for perforations a white female patient became bilaterally blind at the age of 29 years. She also suffered from disabling discomfort in the right dry eye. At the age of 52 a two stage osteo-odonto-keratoprosthesis achieved visual rehabilitation in the left eye and microvascular transplantation of an autologous, submandibular gland resulted in sufficient lubrication to alleviate her severe discomfort in the right eye. As a result of these procedures she was able to take up a regular job again. The total costs of rehabilitation were pound 13 661 which compare with annual gains and regains for society of pound 13 497. An additional pound 4625 was saved annually in guide dog costs. CONCLUSION: This estimate shows that despite the expense of these complex techniques gains are made well within the second year after rehabilitation. In view of the benefit in quality of life for the patient and monetary savings for society these procedures should be funded by national health services at specialist centres.

Adult↗

Stress-activated protein kinase signaling pathways in dry eye and ocular surface disease.

Inflammation is recognized as a key component in the pathogenesis of dry eye and a variety of ocular surface diseases. Stress-activated protein kinases have been identified as pathways signaling ocular surface stresses, such as increased tear film osmolarity and ultraviolet light exposure. Activation of these stress pathways results in transcription of stress related genes, including inflammatory cytokines (e.g. interleukin-1 and tumor necrosis factor (TNF)-alpha and matrix metalloproteinases (MMPs), such as MMP-9. Treatment of osmo-stressed cultured corneal epithelia with inhibitors of the stress associated kinase c-jun N-terminal kinases was found to decrease production of MMPs by these cells. These findings suggest that SAPKs may be key therapeutic targets for dry eye and ocular surface diseases.

Journal Article↗

Ocular surface disease in intensive care unit patients.

PURPOSE: To assess the prevalence and natural history of ocular surface disease in patients in an intensive care unit (ICU) and to identify any predisposing factors in order to improve eye care management protocols. METHODS: The eyes of all patients admitted to an ICU between February and May 1998 were examined at least weekly. The eyelid position, presence of conjunctival oedema, degree of keratopathy and sedation score were documented at every assessment. RESULTS: Twenty-six patients in an ICU were followed throughout their stay, which ranged from 3 days to 10 weeks. Eleven patients (42%) had some degree of keratopathy, which was detected in the majority in the first week of their stay. The presence of ocular surface disease was closely correlated with the degree of lagophthalmos, which in turn is closely related to the depth of sedation or paralysis. CONCLUSIONS: In this first ever longitudinal study it was found that assessment of lid position in ICU patients is the single most important observation to be carried out. A management algorithm derived from this evidence is based on daily observation and selective lid taping and shows encouraging early results.

Adult↗

Conjunctival goblet cell densities in ocular surface disease.

Goblet cell densities were determined in the eyes of normal subjects and in the eyes of patients with various ocular surface diseases using an impression cytological technique. For normal eyes goblet cell densities on the interpalpebral bulbar and inferior palpebral ocular surfaces were 443 (+/- 266 [+/- SD]) and 1,972 (+/- 862) cells millimeter, per square, respectively. All patients in the ocular surface disease groups had decreased goblet cell densities compared with subjects with normal eyes. Compared with normal eyes, eyes with keratoconjunctivitis sicca (KCS) demonstrated a 17% greater goblet cell loss on the interpalpebral bulbar compared with the inferior palpebral ocular surface, while eyes with blepharitis and secondary KCS demonstrated an 8% greater loss on the inferior palpebral surface compared with the interpalpebral bulbar ocular surface. Eyes with cicatricial ocular pemphigoid and Stevens-Johnson syndrome demonstrated greater than 95% goblet cell loss on both the interpalpebral bulbar and inferior palpebral ocular surfaces compared with normal eyes.

Adolescent↗

The role of nitric oxide in ocular surface diseases.

For the first time, the current series of studies provide a possible pathophysiologic mechanism of NO-induced ocular surface disease. NO is present in tear and aqueous humor and is suspected of having an important physiological role in maintaining normal homeostasis of the ocular surface. NO concentrations are higher in aqueous humor compared to tears, though some variability exists between different species. When inflammation was induced by PTK wounding or LPS, three forms of NOS expression were seen in corneal cells. Each isoform of NOS was expressed uniquely according to the specific location of inflammation. When concentrations of NO peaked, the levels of iNOS were markedly increased in fibroblasts and inflammatory cells. The correlation between NO and inflammation was confirmed by treatment with NOS inhibitor, which abrogated the amount of both NO and inflammation. The tissue damage by NO was measured by nitrotyrosine formation. Damage was detected mainly in inflammatory cells, especially those localized in and around the limbal vessel. It is likely that expression of iNOS in limbal fibroblasts has other roles related to survival of limbal stem cells and fibroblasts as well. Because the main source of NO are fibroblasts, we were able to determine the effect of various concentrations of NO on cell viability using a fibroblast culture system. Cell viability increased in dose dependent manner from 10 microM to 500 microM of the NO generator SNAP, but decreased at concentrations above 1000 microM, suggesting that the in vivo mechanism of cell death was indirect, through specific biologic pathways. Therefore, the pathophysiological mechanism of NO action is bimodal with a toxicological component in ocular surface diseases. Furthermore, its concentration and interaction with other oxygen mediators appear to vary depending on the degree of inflammation.

Animals↗

Cultivated corneal epithelial transplantation for severe ocular surface disease in vernal keratoconjunctivitis.

PURPOSE: To report cultivated epithelial transplantation in 2 patients with vernal keratoconjunctivitis (VKC) with severe ocular surface disease. METHODS: Two patients initially diagnosed with burnt-out VKC presented with bilateral photophobia, decreased vision, and corneal neovascularization. The first patient underwent living-related conjunctival-limbal allograft in the left eye and cultivated limbal epithelial cell allotransplant in the right. The second patient underwent unsuccessful amniotic membrane transplantation (AMT) followed by autologous cultivated limbal epithelial cell transplantation in the worse eye. RESULTS: Both patients had onset of VKC in the first decade. Surgical intervention in both led to marked amelioration in symptoms and improvement in vision. In patient 1, vision improved from 20/800 (both eyes) to 20/30 in the right and 20/100 in the left eye at a follow-up of 34 months. In patient 2, it improved from 20/400 to 20/50 after the second procedure, 25 months postoperatively. Histopathology of the excised pannus revealed fibrosis and mononuclear cell infiltrates in all 3 eyes. CONCLUSIONS: Severe ocular surface disease may occur in persistent VKC, leading to marked visual loss. AMT alone may be insufficient to restore the ocular surface, and limbal epithelial cell transplantation is warranted.

Adolescent↗

Fluid-ventilated, gas-permeable scleral contact lens is an effective option for managing severe ocular surface disease and many corneal disorders that would otherwise require penetrating keratoplasty.

PURPOSE: To examine the diagnostic indications and relative merits of a fluid-ventilated, gas-permeable scleral lens for improving vision impaired by irregular astigmatism and for providing a therapeutic environment for managing severe ocular surface disease. METHODS: After a review of scleral lens development and a description of current design and manufacturing innovations, indications for fitting the Boston Scleral Lens were evaluated based on a retrospective review of all available records of patients fitted with this device, and outcome experiences were described. RESULTS: A total of 875 eyes of 538 patients were fitted with the fluid-ventilated, gas-permeable scleral lens during the past 18 years. Most patients were fitted in the past 4 years. Indications included managing severe ocular surface disease and rehabilitating vision impaired by irregular astigmatism associated with corneal disorders. Rigid gas-permeable contact lenses either were not tolerated or were contraindicated in all eyes. Outcomes included improved vision and reduced ocular pain and photophobia associated with severe ocular surface disease. Scleral lenses promoted healing of persistent epithelial defect (PED) refractory to other treatments and prevented PED recurrence in stem cell-deficient and neurotrophic corneas. Microbial keratitis occurred in 4 of 22 eyes treated with extended scleral lens wear for PED after penetrating keratoplasty. CONCLUSIONS: The fluid-ventilated, gas-permeable scleral lens is an important front-line tool for managing many corneal disorders refractory to other treatment measures or otherwise requiring keratoplasty.

Contact Lenses↗

Reliability and validity of the Ocular Surface Disease Index.

OBJECTIVE: To evaluate the validity and reliability of the Ocular Surface Disease Index (OSDI) questionnaire. METHODS: Participants (109 patients with dry eye and 30 normal controls) completed the OSDI, the National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25), the McMonnies Dry Eye Questionnaire, the Short Form-12 (SF-12) Health Status Questionnaire, and an ophthalmic examination including Schirmer tests, tear breakup time, and fluorescein and lissamine green staining. RESULTS: Factor analysis identified 3 subscales of the OSDI: vision-related function, ocular symptoms, and environmental triggers. Reliability (measured by Cronbach alpha) ranged from good to excellent for the overall instrument and each subscale, and test-retest reliability was good to excellent. The OSDI was valid, effectively discriminating between normal, mild to moderate, and severe dry eye disease as defined by both physician's assessment and a composite disease severity score. The OSDI also correlated significantly with the McMonnies questionnaire, the National Eye Institute Visual Functioning Questionnaire, the physical component summary score of the Short Form-12, patient perception of symptoms, and artificial tear usage. CONCLUSIONS: The OSDI is a valid and reliable instrument for measuring the severity of dry eye disease, and it possesses the necessary psychometric properties to be used as an end point in clinical trials.

Diagnostic Techniques, Ophthalmological↗

Conjunctival grafting for ocular surface disease.

The procedure of transplanting healthy conjunctiva onto eyes with damaged ocular surface epithelium was first described by Thoft in 1977. Today, conjunctival autografting is widely used in pterygium surgery and has been shown to be both safe and effective in reducing pterygium recurrence. Several randomized, controlled, clinical trials have been reported in the literature, and conjunctival autografting is now recognized to have an efficacy equal to that of such adjunct therapies as beta-irradiation and mitomycin C, and yet it is safer than these treatments. Recent modifications of the conjunctival autograft include the conjunctival rotation autograft and the inferior conjunctival transposition flap, both of which have been reported to be associated with low rates of recurrence. With the discovery of the role of limbal stem cells in the maintenance and stability of the corneal surface, recent forms of ocular surface transplantation that have supplanted Thoft's conjunctival transplantation procedure include limbal autograft transplantation and limbal allograft transplantation. In addition, the adjunct use of human amniotic membrane in these ocular surface transplantation procedures has improved success and survival rates in the management of ocular surface disease, which still presents significant challenges to clinicians today.

Amnion↗

[Fresh amniotic membrane transplantation for ocular surface diseases].

OBJECTIVE: To evaluate the therapeutic effects of fresh amniotic membrane transplantation for ocular surface disorders (OSDs). METHODS: Fresh amniotic membrane transplantation was performed in 38 cases (52 eyes) of ocular surface diseases, including pterygium, recurrent pterygium, Mooren's ulcer, Viral keratitis, and symblepharon. Follow-up studies ranging from 3 to 12 months were conducted. RESULTS: No acute graft rejection was observed following the operation in these cases, and no recurrence was found in cases of pterygium and corneal ulcer during the follow-up period. The ocular movement was restored for the eyes with severe symblepharon. CONCLUSION: Fresh amniotic membrane can be used as a graft material for ocular surface reconstruction, in which complete removal of the pathological tissues and reliable fixation of the amniotic membrane graft are crucial steps.

Adult↗

Chronic ocular surface disease after allogeneic bone marrow transplantation.

Graft-versus-host disease (GVHD) is a common complication of allogeneic bone marrow transplantation (allo-BMT). Ocular surface disease (OSD) is one of the most common manifestations of chronic ocular GVHD, yet little is known about it. In this article, we review the available literature on this condition and present results from our study of the manifestations of OSD in the chronic phase (>3 months duration) post allo-BMT. Our study consisted of a retrospective chart review of 62 allo-BMT patients with chronic OSD evaluated at our center between 1995 and 2002. The clinical features, systemic associations, treatment, and status of OSD at the last follow-up are presented and discussed in the context of other reports of OSD in GVHD.

Journal Article↗

Cultured corneal epithelia for ocular surface disease.

PURPOSE: To evaluate the potential efficacy for autologous and allogeneic expanded corneal epithelial cell transplants derived from harvested limbal corneal epithelial stem cells cultured in vitro for the management of ocular surface disease. METHODS: Human Subjects. Of the 19 human subjects included, 18 (20 procedures) underwent in vitro cultured corneal epithelial cell transplants using various carriers for the epithelial cells to determine the most efficacious approach. Sixteen patients (18 procedures on 17 eyes) received autologous transplants, and 2 patients (1 procedure each) received allogeneic sibling grafts. The presumed corneal epithelial stem cells from 1 patient did not grow in vitro. The carriers for the expanded corneal epithelial cells included corneal stroma, type 1 collagen (Vitrogen), soft contact lenses, collagen shields, and amniotic membrane for the autologous grafts and only amniotic membrane for the allogeneic sibling grafts. Histologic confirmation was reviewed on selected donor grafts. Amniotic membrane as carrier. Further studies were made to determine whether amniotic membrane might be the best carrier for the expanding corneal epithelial cells. Seventeen different combinations of tryspinization, sonication, scraping, and washing were studied to find the simplest, most effective method for removing the amniotic epithelium while still preserving the histologic appearance of the basement membrane of the amnion. Presumed corneal epithelial stem cells were harvested and expanded in vitro and applied to the amniotic membrane to create a composite graft. Thus, the composite graft consisted of the amniotic membrane from which the original epithelium had been removed without significant histologic damage to the basement membrane, and the expanded corneal epithelial stem cells, which had been applied to and had successfully adhered to the denuded amniotic membrane. Animal model. Twelve rabbits had the ocular surface of 1 eye damaged in a standard manner with direct removal of the presumed limbal stem cells, corneal epithelium, and related epithelium, followed by the application of n-heptanol for 60 seconds. After 6 weeks, all damaged eyes were epithelialized and vascularized. Two such treated eyes were harvested without further treatment, to be used for histologic study as damaged controls. The remaining 10 rabbits received composite grafts (consisting of amniotic membrane with expanded allogeneic rabbit corneal epithelial cell transplants) applied to the ocular surface in a standard manner followed by the application of a contact lens. At 16 days following transplantation, 5 of the rabbits were sacrificed and the corneal rims were removed for histologic study. At 28 days, the remaining rabbits were sacrificed and the previously damaged eyes were harvested for histologic and immunohistochemical study. RESULTS: Human subjects. Of the 19 total patients admitted to the study, the presumed corneal epithelial stem cells of 1 patient did not grow in vitro. Of the remaining 18 patients (20 procedures, 19 eyes), 3 patients had unsuccessful results (3 autologous procedures), 1 patient had a partially successful procedure (allogeneic procedure), and 1 patient had a procedure with an undetermined result at present (allogeneic procedure). One unsuccessful patient had entropion/trichiasis and mechanically removed the graft and eventually went into phthisis. The other 2 unsuccessful patients suffered presumed loss of autologous donor epithelium and recurrence of the ocular surface disease (pterygium). The partially successful patient receiving an allogeneic transplant had infectious keratitis delay of his re-epithelialization; he has only minimal visual improvement but has re-epithelialized. The patient receiving the second allogeneic graft lost his donor epithelium at day 4. Additional donor epithelium was reapplied, but the result is undetermined at present. Amniotic membrane as carrier. The in vitro preparation of the amniotic membrane with corneal epithelial stem cell graft overlay was successful. Histology documented removal of the amniotic epithelium and reapplication of corneal epithelial cells. Animal model. The 2 rabbits that had no reparative surgery following standard ocular surface injury had histology and immunopathology consistent with incomplete corneal epithelial stem cell failure with vascularization and scarring of the ocular surface. Light microscopy and immunohistologic staining with AE5 confirmed the conjunctival phenotype of the ocular surface repair but also documented the incomplete model. The allogeneic stern cell transplants had varying results. One rabbit had a suppurative infection and lost the graft. Reparative surgery failed in 2 of the rabbits, failed partially in 3 of the rabbits, was partially successful in 3 others, and was successful in 1 rabbit at 28 days. Histologic and immunopathologic study documented successful growth of corneal epithelium onto the recipient surface. CONCLUSIONS: 1. Presumed corneal epithelial stem cells can be harvested safely from the limbus and expanded successfully in vitro. 2. Expanded corneal epithelial cell cultures can be grown onto various carriers, but currently denuded amniotic membrane seems to be the best carrier for ocular surface repair. 3. Expanded corneal epithelial cell transplants appear to resurface damaged ocular surfaces successfully, but cellular tracking and further confirmation are required. 4. Expanded allogeneic corneal epithelial cell transplants are technically possible and may represent alternative treatment modalities for selected ocular surface problems. 5. These techniques potentially offer a new method of restoring a normal ocular surface while minimizing the threat of damage or depletion to the contralateral or sibling limbal corneal epithelial stem cells. 6. The rabbit model was probably incomplete and should be interpreted with caution. The complete eradication of all corneal epithelial stem cells from any eye is difficult, making confirmation of such work challenging. 7. The results of the rabbit model suggest that allogeneic grafts may restore a nearly normal ocular epithelial surface to certain ocular surface injuries.

Adult↗

Comparison of autologous serum eye drops with conventional therapy in a randomised controlled crossover trial for ocular surface disease.

AIMS: To evaluate the efficacy of 50% autologous serum drops against conventional treatment in ocular surface disorders refractory to normal treatments in a prospective randomised crossover trial. METHOD: Patients fulfilling ophthalmological and haematological entry criteria were randomised to either 3 months of autologous serum 50% followed by 3 months of their conventional treatment, or 3 months of conventional treatment, followed by 3 months of autologous serum. Clinical assessments, including Schirmer's test, rose Bengal, and fluorescein staining, were carried out on entry and at monthly intervals. Impression cytology was performed at entry, 3 and 6 months. Grading was carried out on degrees of squamous metaplasia and goblet cell density. Subjective comfort was recorded daily using the "faces" scale. These categorical scores were converted to linear measurement using Rasch analysis. Statistical analysis was carried out using Wilcoxon's signed rank test and ANOVA. RESULTS: 16 patients were recruited with 31 eyes studied. The ocular surface diseases chiefly included Sjögren's syndrome (n = 6) and keratoconjunctivitis sicca (n = 5). Impression cytology available in 25 of 31 eyes showed significant improvement on serum treatment, p<0.02. Rasch weighted faces scores were statistically significantly better with serum, p<0.01. CONCLUSION: The results of this randomised study provide further evidence of the beneficial effects of autologous serum in severe ocular surface disorders. For most of these patients, autologous serum was superior to conventional treatment for improving ocular surface health and subjective comfort.

Adult↗

Use of autologous cultured limbal and conjunctival epithelium in a patient with severe bilateral ocular surface disease induced by acid injury: a case report of unique application.

PURPOSE: Reconstruction of the ocular surface in a case of severe bilateral partial limbal stem cell deficiency (LSCD) with extensive symblephara using autologous cultured conjunctival and limbal epithelium. CASE REPORT: A 31-year-old woman presented with severe bilateral ocular surface disease with partial limbal stem cell deficiency, symblephara, lid and facial scarring, with a vision of 20/400 and counting fingers at 1 m in both eyes. Limbal and conjunctival tissue was harvested from the healthy-appearing left eye and used to generate two sheets of composite epithelium consisting of central limbal and peripheral conjunctival cells. The limbal tissues were explanted in the central region while the conjunctival tissues were explanted on the periphery of the deepithelialized human amniotic membrane (HAM) and nurtured using human corneal epithelial cell medium. After successful generation of a monolayer from both tissues had been confirmed, the composite of cultivated limbal and conjunctival epithelium with HAM was transplanted in each eye after excision of fibrous tissue and release of symblephara. One year postoperatively, the patient had a best spectacle-corrected visual acuity of 20/40 in the right eye (preoperative acuity 20/400) and counting fingers at 1 m in the left eye (same as preoperative) with a stable ocular surface. CONCLUSIONS: Autologous cultured epithelial transplantation is as an excellent option in selected patients with bilateral partial LSCD with small area(s) of healthy limbus in either eye and avoids the attendant risk of rejection and cost and potential toxicity of immunosuppression in allogeneic tissue transplantation. This case also highlights the feasibility of generating a composite culture of limbal and conjunctival epithelium using a single amniotic membrane.

Acids↗

Incidence and prevalence of glaucoma in severe ocular surface disease.

PURPOSE: To describe the incidence and prevalence of glaucoma in a patient population with severe ocular surface disease (OSD). METHODS: A retrospective case series was compiled from all charts of patients in the Cincinnati Eye Institute/University of Cincinnati and University of Minnesota population with a diagnosis of severe OSD from 1991 to 2003. The incidence and prevalence of glaucoma in the overall patient population were identified, and stratified into disease subgroups. RESULTS: Of the 108 eyes evaluated in this study, 71 were diagnosed with glaucoma. The overall prevalence of glaucoma in patients with severe OSD is 65.7%, with a range from 42.9% to 88.4%. Analysis by subgroup shows the highest percentage of patients with concurrent glaucoma fall into the categories of aniridia and chemical injury, and the lowest was noted in those patients with autoimmune or iatrogenic OSD. Overall, the incidence of glaucoma was 20.4%, with a range of 13.6% to 60%. CONCLUSIONS: Compared with previous studies, our results show a significantly higher prevalence of glaucoma in patients with severe OSD. This information warrants increased attention to treatment and management of OSD and concurrent glaucoma.

Adolescent↗