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PubMed2003

The Boston Scleral Lens in the management of severe ocular surface disease.

Fluid-ventilated, gas-permeable scleral lenses are a valuable front-line tool in the management of severe ocular surface disease. In addition to enhancing vision, they have the potential to reduce greatly the disabling ocular pain and photophobia associated with SJS, TEN, and ocular cicatricial pemphigoid. They are also useful in healing some PEDs that are refractory to all other treatment strategies and in reducing PED recurrence in stem cell-deficient and neurotrophic corneas. The therapeutic benefits of these lenses are provided by the oxygenated aqueous environment they create over the corneal epithelium. The oxygenated precorneal fluid compartment that is maintained at neutral pressure protects the epithelial surface from the desiccating effects of exposure to air and the friction generated by blinking and avoids the shearing forces generated during the blink-induced movement of soft lenses.

Contact Lenses↗

PubMed2005

Methodologies for the study of ocular surface disease.

The ability to obtain reliable results from clinical trials of therapies for ocular allergic disease and dry eye disease is often limited because of inadequate control of variables, such as environment, patient life style, compliance, and individual fluctuations that occur from one assessment visit to another. The controlled allergen challenge (CAC) model of allergic conjunctivitis allows signs and symptoms of the disease to be elicited in a physiologically accurate and reproducible manner. The rigid criteria for subject selection, the controlled allergic reaction, and the standardized and quantified grading systems allow for a reproducible baseline from which statistically and clinically significant differences between formulations can be assessed. Similarly, the controlled adverse environment (CAE) model for dry eye mimics the environmental stimuli that lead to ocular surface drying. Preselected subjects have a reproducible, homogeneous baseline reaction from which the effects of various treatments can be significantly evaluated and compared. CAC and CAE provide accurate means to study highly variable and individual ocular surface disease.

Journal Article↗

PubMedDate not supplied

Ocular surface disease in atopic dermatitis.

PURPOSE: To describe the ocular surface disorders of 362 patients with severe active atopic dermatitis (AD) treated in the Ophthalmology Department of Kobe University Hospital and Kobe Rosai Hospital Eye Clinics during the period 1994-1996. METHODS: Routine ophthalmic examinations as well as tear film break-up time (BUT) and Schirmer tests were carried out. RESULTS: Lid eczema (65.7%), atopic keratoconjunctivitis, and superficial punctate keratopathy (67.5%) were the dominant ocular diseases in these patients. Tear function tests showed a BUT value of less than 10 seconds in 62.4% of the eyes and a Schirmer test value of less than 5 mm in 56.2% of the eyes. CONCLUSIONS: A careful examination of the ocular surface is essential in treating AD patients. We also suggest that the ocular surface disorders in AD may be due to allergic reactions and disorders in tear film quantity or quality.

Adolescent↗

PubMed1988

Toxic endothelial degeneration in ocular surface disease treated with topical medications containing benzalkonium chloride.

We examined a 56-year-old man with keratoconjunctivitis sicca and marked ocular surface disease in whom the prolonged frequent use of topical medications containing the preservative benzalkonium chloride was associated with corneal endothelial damage requiring corneal transplantation in one eye. The histopathologic findings on examination of the excised button were consistent with toxic endothelial disease. Postoperatively, the patient's symptoms continued until the preservative-containing medications were substituted with nonpreserved saline eyedrops.

Benzalkonium Compounds↗

PubMed2004

[Keratolimbal allografts and multilayer amniotic membrane transplantation in the treatment of ocular surface disease due to chemical burns].

PURPOSE: To analyze the functional effect and to present the technique of keratolimbal allograft and multilayer amniotic membranetransplantation for the treatment of ocular surface disease after heavy chemical burn. MATERIAL AND METHODS: Treatment comprised 3 eyes of 2 patients suffering form ocular surface deficiency after chemical (acid) burn. Surgeries were provided under local anesthesia. After circumferential peritomy and removal of fibrovascular layer, stem cells in the fashion of keratolimball crescent allograft, following by multilayer amniotic membrane transplantation were performed. RESULTS: 3 months after surgery the corneal surface was covered with fully differentiated epithelium in all patients. In two of three patients, improvement of the visual acuity was also observed. However, in one eye despite good epithelium maintenance the stroma was still not transparent. CONCLUSION: Keratolimbal allograft with multilayer amniotic transplantation is interesting method of ocular surface reconstruction. Combined procedure with use of two different tissues seems to be relevant among patients with bilateral ocular surface dysfunction with complete destruction of stem cells after chemical burn.

Amnion↗

PubMed2003

Lacrimal histopathology and ocular surface disease in a rabbit model of autoimmune dacryoadenitis.

PURPOSE: To study the effects of induced autoimmune dacryoadenitis on lacrimal gland function, histopathology, and ocular surface disease in a rabbit model. METHODS: One lacrimal gland was surgically excised from each experimental rabbit, and epithelial cells were purified, cultured, irradiated, and then cocultured with autologous peripheral blood lymphocytes (PBLs) for 5 days. Autoimmune dacryoadenitis was induced by injecting the autologous mixed cell reactions (AMCRs) into the rabbit's remaining lacrimal gland. Normal rabbits and rabbits with both lacrimal glands injected with nonstimulated PBLs were examined as controls. Eyes were evaluated biweekly for 8 weeks by slit-lamp biomicroscopy, Schirmer testing, tear break-up time measurement, and rose bengal examination. Sections of lacrimal glands removed at 8 weeks post-operation were immunostained using antibodies against rabbit class II major histocompatibility complex molecule (MHC-II), CD4, CD8, CD18, and rabbit thymic lymphocyte antigen (RTLA). Relative numbers of positively stained cells were quantified with a ChromaVision image analysis system. RESULTS: During an 8-week period, a continuous decrease in tear production and stability, accompanied by a continuous increase in rose bengal staining, occurred in eyes in which AMCR-PBL had been injected into the ipsilateral lacrimal glands. Similar, though generally less severe, changes occurred in eyes contralateral to the AMCR-PBL-injected eyes. No obvious changes by 8 weeks in these parameters were found in eyes in which the lacrimal glands had been injected with nonstimulated PBLs or in the lacrimal gland-excised eyes contralateral to normal eyes. Interstitial cells in normal lacrimal glands expressed CD18 and RTLA antigens, but few expressed CD4, CD8, or MHC-II. Focal mononuclear cell infiltrates were only found in lacrimal glands from animals with induced autoimmune dacryoadenitis. These cells were predominantly positive for CD4 (7.3-fold increase), RTLA (7.8-fold increase), or CD18 (42-fold increase). MHC-II expression in interstitial and ductal epithelial cells was also significantly greater in these animals than in control animals. The mononuclear cell infiltrates were frequently found enveloping venules, some of which appeared to be high endothelial cell venules. The ductal epithelium also contained CD4 and CD8 immunopositivity, within the epithelium, at the lumenal surface, or surrounding the ducts. Occasionally CD4 and CD8 immunopositive cells could be identified within the acinar lumens. CONCLUSIONS: Injection of activated PBLs (i.e., AMCR-PBLs) in the lacrimal gland induces autoimmune dacryoadenitis with immunopathologic features similar to those of Sjögren's syndrome. The lacrimal immunopathology is accompanied by typical clinical manifestations of dry eye syndrome. The persistent significant dry eye does not appear to result just from failure of the diseased gland but from a more general dysfunction of the surface secretory tissues.

Animals↗

PubMed2005

Intraoperative mitomycin C and amniotic membrane transplantation for fornix reconstruction in severe cicatricial ocular surface diseases.

PURPOSE: To investigate whether intraoperative application of mitomycin C may enhance the success of amniotic membrane transplantation in symblepharon lysis and fornix reconstruction in severe cicatricial ocular surface diseases. DESIGN: Noncomparative interventional case series. PARTICIPANTS: Sixteen patients (8 female, 8 male; 18 eyes) with a mean age of 41+/-23.4 years (range, 3-79) and suffering from severe chemical/thermal burns (7 eyes), multiple recurrent pterygia and pseudopterygia (5 eyes), Stevens-Johnson syndrome (4 eyes), and ocular cicatricial pemphigoid (2 eyes) were consecutively enrolled. All except for 2 eyes had had prior surgical attempts of surgical reconstruction, including 6 eyes with a mucous membrane graft (MMG), but still presented with symblepharon and persistent ocular surface inflammation. INTERVENTION: After excision of subconjunctival fibrovascular tissues, 0.04% mitomycin C was applied for 5 minutes in the deep fornix before amniotic membrane transplantation. MAIN OUTCOME MEASURES: Deeper fornix, noninflamed ocular surface, and full motility. RESULTS: The mean epithelial healing time was 4.2+/-1.9 weeks. During the follow-up of 14.16+/-5.2 months, all eyes showed a marked reduction of conjunctival inflammation, a deep fornix, and a continuous tear meniscus. Of 12 eyes with motility restriction, 2 eyes with multiple recurrent pterygia and 1 eye with severe thermal burn showed recurrence of partial motility restriction 2 months after surgery. The vision of 9 eyes was successfully restored by an additional keratolimbal allograft with subsequent penetrating keratoplasty (6 eyes). CONCLUSION: Intraoperative application of mitomycin C is an effective means to reduce chronic and deep-seated conjunctival inflammation, and helps amniotic membrane restore a deep fornix after symblepharon lysis, even in eyes that had a failed MMG. Restoration of deep fornix and tear meniscus is an important prerequisite to achieve successful reconstruction by subsequent limbal stem cell transplantation.

Adolescent↗

PubMed1979

Tear osmolarity and ocular surface disease in keratoconjunctivitis sicca.

Tear osmolarity and Rose Bengal staining were studied in a group of patients with keratoconjunctivitis sicca (KCS) before and after treatment with isotonic and one-half isotonic saline to compare treatment with these two solutions and to ascertain whether tear film osmolarity could be correlated with ocular surface disease. When 20 KCS eyes were treated with isotonic saline drops every three hours for one week, the average (+/-SD) tear osmolarity decreased from 365 +/- 77 mOsm/L to 329 +/- 47 mOsm/L, and the average (+/-SD) Rose Bengal staining score decreased from 4.1 +/- 3.1 to 3.6 +/- 3.3. There was no objective difference between treatment with isotonic and one-half isotonic solutions, in a double-masked comparison, however, four of five patients with diagnostically significant Rose Bengal staining preferred the half isotonic solution. There was a significant positive correlation between tear film osmolarity and Rose Bengal staining.

Aged↗

PubMed2005

X-linked anhidrotic ectodermal dysplasia disruption yields a mouse model for ocular surface disease and resultant blindness.

X-linked anhidrotic/hypohidrotic ectodermal dysplasia (EDA) is caused by mutations in the (EDA) gene, which is required for the morphogenesis of ectoderm-derived tissues. Although EDA function in skin appendage development has been studied in Eda mutant "Tabby" mice, we have recently identified characteristic abnormalities in the ocular surface, an ectoderm-derived tissue. Histology of eyes of Tabby males revealed that 1) as previously reported, mice lacked meibomian glands; 2) >80% developed corneal lesions such as neovascularization, keratitis, ulceration, and keratinization identifiable from 9 weeks of age; and 3) > 80% showed ocular surface inflammation (blepharitis and conjunctivitis) when housed in a standard environment. Strikingly, both corneal defects and inflammation were prevented in Tabby mice bearing a transgene for the Eda-A1 isoform, but meibomian glands were restored little if at all. These findings suggest that intact ocular surface health is EDA dependent and that Tabby corneal abnormalities are not solely dependent on meibomian gland lipid secretion. Alternatively, susceptibility to inflammation and other phenotypes could result from failure of the usual EDA receptor to activate nuclear factor-kappaB transcription factors. This can be further tested in Tabby and Tabby-EDA transgenic mice, which provide unique models of severe ocular surface disease.

Animals↗

PubMed2006

Successful management of aniridic ocular surface disease with long-term bandage contact lens wear.

PURPOSE: To present an aniridic patient with failed penetrating keratoplasties OU (PK) who underwent successful repeat PK OD, which has remained clear for 4 years with continuous bandage lens (BCL) wear. METHODS: A 73-year-old aniridic woman who had a failed PK complicated by ocular surface disease refused limbal stem cell transplantation and underwent repeat PK in her right eye. The immediate postoperative course was uneventful except for mild irregularity of the graft epithelium. Two months postoperatively, she presented with an epithelial defect along the inferotemporal graft margin adjacent to an exposed, loose interrupted suture. The suture was removed, and although the initial epithelial defect healed, she suffered recurrent episodes of epithelial breakdown and generalized whorl epitheliopathy. A BCL was inserted and rendered prompt healing of the graft epithelium, which has remained smooth and intact for 4 years. RESULTS: The graft remains thin and clear with a smooth and intact epithelial surface beneath the BCL and no signs of limbal stem-cell deficiency. CONCLUSION: Long-term BCL wear provided good corneal transplant surface protection in an aniridic patient with recurrent epithelial breakdown, thereby sparing the need for limbal stem cell transplantation and the use of potentially toxic systemic immunosuppressive therapy. Meticulous follow-up is required to monitor contact lens loss and epithelial breakdown as well as signs of secondary infectious keratitis.

Aged↗

PubMed2001

[Amniotic membrane graft in ocular surface disease. Prospective study with 31 cases].

INTRODUCTION: Amniotic membrane's unique combination of properties including the facilitation of migration of epithelial cells, the reinforcement of basal cellular adhesion and the encouragement of epithelial differentiation [6] together with its ability to modulate stromal scarring and its anti-inflammatory and anti-bacterial activity has led to its use in the treatment of ocular surface pathology as well as an adjunct to stem cell grafts of the corneal limbus [6-4]. We report a prospective study of 30 patients so treated. MATERIAL AND METHODS: We studied 31 eyes of 30 patients subjected to amniotic membrane grafts between September 1999 and May 2000. There were 25 men and 5 women with an average age of 60.1 (range 25-86) years who were followed for a mean of 7.7 (range 4-11) months. 5 groups (A to D) were observed: A: 6 eyes. Small chronic ulcers without limbal involvement. B: 4 eyes. Ulcers of at least 75% corneal area or occupying 75% of the limbus. C: 9 eyes. Corneal burns. D: 8 eyes. Painful bullous corneal dystrophies unresponsive to other treatment. E: 4 eyes. Symblepharons. Amniotic membrane was placed on the corneal lesion, epithelial surface externally [6, 15], trimmed and sutured with interrupted 10/0 nylon, removed at one month. In two patients (11, 12) inflamed conjunctiva was recessed and amnion sutured to the recessed margin. For the bullous dystrophies we removed all the corneal epithelium and either sutured the amnion to peri-limbal conjunctiva (4 eyes) or to the limbus (4 eyes). For the symblepharons the conjunctiva was dissected to reform the fornix which was lined with amniotic membrane, sutured with 8/0 vicryl. Patients were reviewed regularity. RESULTS: Group A: All healed within 15 days, in most with dissolution of the amnion over 2-3 months although some persisted, covered with corneal epithelium. An eye with a Descemetocoele and one with a microperforation both healed. Vision improved more than two lines in 4 of 6 eyes. Group B: 2 of 4 eyes healed, one despite detachment of the membrane after 15 days. One eye was salvaged by tarsorrhaphy over a fresh keratoplasty after perforation of a neuroparalytic ulcer on failure of three successive amnion grafts. The final cornea vascularised despite an amnion graft for a meta-herpetic ulcer. Group C: 2 of 9 eyes had limbal damage in one quadrant but 7 had vessels in at least three-quarters of the circumference. One (15) also had a limbal autograft. 3 of 9 eyes healed satisfactorily with more than 2/10 improvement in acuity in each case. 2 showed further neovascularisation despite surface healing. One old chemical burn healed satisfactorily but vascularisation remained 5 eyes failed to heal with lysis of the graft, the patient who had a limbal autograft developed a vascular pannus, and in 4 eyes neovascularisation progressed to cover the entire cornea. Group D: 3 eyes settled with loss of symptoms but in 5 the graft detached within 15 days. All eyes where the membrane had been sutured to the conjunctiva beyond the limbus failed whilst 3 of 4 in which it had been sutured anterior to the limbus succeeded, leaving a persistent whitish membrane under the epithelium. Group E: We were able to reconstruct the cul de sac in 3 out of 4 eyes. In one patient with recurrent pterygium good ocular movement was restored, previously limited by scarring. One with associated ocular surface damage from a thermal burn failed by scarring of the cul de sac a month after surgery. DISCUSSION: Our best results were in persistent trophic ulcers of the cornea (Groups A and B) with a success rate of 80%, comparable to those of others [49, 37, 38]. The ready availability of amniotic membrane in our facility makes amniotic membrane transplantation the main secondary treatment for such lesions, especially because of the visual improvement we obtained. Because we did not observe any improvement in corneal thickness after this treatment we advise its early use before significant stromal lysis. The technique was not sufficient to control the effect of corneal anaesthesia in two eyes [40] or in chemical burns suggesting that amniotic membrane alone is insufficient to promote corneal healing in the absence of limbal stem cells. Nevertheless, three eyes did benefit. It has been suggested [13] that the anti-apoptotic function of amnion may prevent stem cell loss in such eyes [42], thus it appears logical to offer an amniotic membrane graft first, before stem cell transplantation, which may entrain complications in the donor eye if autografted [43] or because of the rejection risk of an allograft. It may be that an amniotic membrane graft simply becomes a holding procedure allowing time to settle the eye so as to allow secondary procedures to address the underlying cause of further damage. Our treatment of bullous dystrophy only succeeded on confining the graft to within the limbus, 3 out of 4 eyes becoming comfortable. By contrast we found amniotic membrane helpful in reconstructing symblepharons in the absence of local inflammation. CONCLUSION: Amniotic membrane grafting is a simple and straightforward surgical technique which should form part of the therapeutic arsenal for the treatment of ocular surface disease. Indications for the technique need further clarification for it is evident that it cannot correct all secondary pathology associated with limbal destruction. It is certainly preferable to conjunctival advancement and has proved useful in the reconstruction of the cul-de-sac.

Adult↗

PubMed2006

Cytokeratin 15 can be used to identify the limbal phenotype in normal and diseased ocular surfaces.

PURPOSE: To elucidate the expression pattern of K15, K19, K14, and K12 in human and mouse ocular surface epithelium as putative markers of epithelial phenotype. METHODS: Immunohistochemical staining with specific antibodies for K15, K19, K14, and K12 was performed in human donor cornea tissue and normal ICR mouse corneas, with emphasis on localization of immunopositive cells. Immunohistochemistry was performed in a limbus-deficient mouse model as well as in clinical samples of pannus surgically removed from a thermal burn and a patient with Saltzmann's dystrophy. Staining patterns were classified as limited to the most basal layer (K(bas)), basal and suprabasal layers (K(bas-sup)), predominantly in suprabasal layers (K(sup)) and negative staining (K(-)). RESULTS: In human conjunctival epithelium, strong expression of K15 was observed in basal cells, whereas K19 was expressed in both basal and suprabasal layers (K15(bas)/K19(bas-sup)/K12(-)). Limbal epithelial cells were K15(bas-sup)/K19(bas-sup)/K12(sup), whereas epithelial cells in the central cornea were K15(-)/K19(bas-sup)/K12(bas-sup). In contrast, the mouse ocular surface demonstrated a different expression pattern of K15 and K19 than did the human tissue in the conjunctiva (K15(bas-sup)/K19(bas)/K12(-)) and the limbus (K15(bas-sup)/K19(bas)/K12(sup)). Neither K15 nor K19 was expressed in the central mouse cornea (K15(-)/K19(-)/K12(bas-sup)). Similar cytokeratin expression was observed in conjunctivalized corneas in mice and in surgically removed pannus tissue. CONCLUSIONS: Although the expression of K15 and K19 differ in humans and mice, specific staining patterns can be used to characterize the epithelial phenotype in normal and diseased ocular surface.

Animals↗

PubMed1983

Goblet cell density in ocular surface disease. A better indicator than tear mucin.

Mucinlike glycoprotein from tears and conjunctival goblet cell densities were determined in normal subjects and in patients. The results indicated that although there was a statistically significant decrease, a substantial amount of mucinlike glycoprotein was present in tears from patients with ocular cicatricial pemphigoid (OCP), radiation keratitis, and corneal anesthesia. In the same patients, the goblet cell count was profoundly decreased in OCP and radiation keratitis, well out of proportion to the modest fall in mucinlike glycoprotein. This indicated that the tear mucin content shows minimal variation over a great variation in goblet cell density, suggesting that while moderate mucin deficiency may be associated with surface abnormalities, such mucin deficiency may not be the only cause of the ocular surface epithelial problems characteristic of these diseases. In addition, it is proposed that the goblet cell content of the conjunctiva is a sensitive indicator of primary ocular surface disease.

Cell Count↗

PubMed2003

Successful regrafting of cultivated corneal epithelium using amniotic membrane as a carrier in severe ocular surface disease.

PURPOSE: Our group performed cultivated allogeneic corneal epithelial transplantation in 13 eyes from 11 patients with severe ocular surface disorders. After the clinical application of this new surgical treatment, some patients experienced epithelial and subepithelial opacities. We applied our procedure again in these patients to achieve successful ocular surface reconstruction. METHODS: The corneal limbal epithelial cells from donor corneas were cultivated for 4 weeks on denuded amniotic membrane (AM) carrier, with 3T3 fibroblast coculture and airlifting. The study subjects consisted of 3 patients. At 3 and 12 months after the first operation, the failed epithelial graft with AM was replaced with new allogeneic corneal epithelium cultivated on AM. RESULTS: At 48 hours after transplantation, the corneal surfaces of the 3 eyes were clear and smooth; the entire corneal surfaces were evenly covered with the transplanted cultivated corneal epithelium, which did not stain with fluorescein. The ocular surface epithelia of these patients are all stable without epithelial defects. CONCLUSIONS: We have shown that, in cases where the initially transplanted cultivated epithelium becomes opaque, it is possible to repeat the transplantation process with new cultivated epithelium on AM.

Adult↗

PubMed2004

Amniotic membrane transplantation in the management of severe ocular surface disease: indications and outcomes.

Since 1995, with the availability of cryopreserved amniotic membrane (AM), the use of AM as a patch or graft for ocular surface reconstruction has become recognized as an important alternative for treatment of persistent epithelial defects and sterile ulceration that are refractory to conventional therapy. A major problem with evaluating the efficacy of AM transplantation is the lack of controlled clinical studies. Moreover, for some diseases there is no accepted "standard" therapy, and the incidence of the disease is too low to allow proper randomization. In this review, we have attempted to assess the indications and outcomes of AM transplantation based on 661 cases reported in the peer-reviewed literature. Successful outcome was defined as the healing of an epithelial defect (corneal or conjunctival) over a specified time period and the lack of induced motility disturbance.

Journal Article↗

PubMed1998

Cytokines and tear function in ocular surface disease.

In summary, tear EGF levels correlate most strongly with tear production in normals, and it is likely that some form of homeostatic mechanism exists to provide a constant supply to the ocular surface. Commercial ELISA kits appear to measure EGF in tears with good consistency and may be useful in the future to improve comparability of data from different studies. In addition, in ocular rosacea, which mimics keratoconjunctivitis sicca in a number of respects, there is a differential increase in the level of the inflammatory cytokine IL-1 alpha in the tear fluid. Much of this elevation appears to be the result of reduced tear turnover, which may form an important positive feedback mechanism encouraging tear stagnation and the perpetuation of ocular surface inflammation.

Adult↗

PubMed2005

Radiotherapy-induced ocular surface disease.

Today radiation is routinely used as a therapeutic modality for select tumors of the orbit, adnexa, paranasal sinus, and nasopharynx. Despite significant improvements in mechanisms of delivery and protective shielding, acute and chronic complications of radiation can affect different segments of the eye. In this report, we provide an overview of ocular damage secondary to radiotherapy. We identify the characteristic clinical changes and underlying pathophysiologic mechanisms involving the ocular surface and provide a rational approach to their prevention and treatment.

Eye↗

PubMed2005

[What's new in ocular surface disease?].

The 76th meeting of the Association for Research in Vision and Ophthalmology (ARVO) was held in Fort Lauderdale, Florida on 25-29 April 2004. The congress focused on the latest developments in clinical and laboratory research in ophthalmology and the treatment of ocular disease. In this article the authors review new insights into dry eye, including recent treatment developments, discuss current advances in the field of ocular allergy and highlight new findings in the area of ocular infection presented at the ARVO meeting.

Animals↗