Yonca A. Akova

Role of Hyperosmolarity in the Pathogenesis and Management of Dry Eye Disease: Proceedings of the OCEAN Group Meeting

Dry eye disease (DED), a multifactorial disease of the tears and ocular surface, is common and has a significant impact on quality of life. Reduced aqueous tear flow and/or increased evaporation of the aqueous tear phase leads to tear hyperosmolarity, a key step in the vicious circle of DED pathology. Tear hyperosmolarity gives rise to morphological changes such as apoptosis of cells of the conjunctiva and cornea, and triggers inflammatory cascades that contribute to further cell death, including loss of mucin-producing goblet cells. This exacerbates tear film instability and drives the cycle of events that perpetuate the condition. Traditional approaches to counteracting tear hyperosmolarity in DED include use of hypotonic tear substitutes, which have relatively short persistence in the eye. More recent attempts to counteract tear hyperosmolarity in DED have included osmoprotectants, small organic molecules that are used in many cell types throughout the natural world to restore cell volume and stabilize protein function, allowing adaptation to hyperosmolarity. There is now an expanding pool of clinical data on the efficacy of DED therapies that include osmoprotectants such as erythritol, taurine, trehalose and L-carnitine. Osmoprotectants in DED may directly protect cells against hyperosmolarity and thereby promote exit from the vicious circle of DED physiopathology.

Penetrating Keratoplasty in Cicatrizing Conjunctival Diseases

PURPOSE The outcome of successful penetrating keratoplasty (PK) typically is poor in eyes with end-stage chronic cicatrizing conjunctival diseases such as ocular cicatricial pemphigoid (OCP), Stevens-Johnson syndrome, and toxic epidermal necrolysis due to immunologically driven conjunctival inflammation associated with conjunctival cicatrization and lid abnormalities, severe dry eye, and extensive corneal neovascularization. The authors report the results of their experience with PK in 13 patients with OCP, Stevens-Johnson syndrome, and toxic epidermal necrolysis. METHODS The authors reviewed the records of patients with OCP, Stevens-Johnson syndrome, or toxic epidermal necrolysis seen between 1976 and 1992. Patients who underwent PK were examined for the purpose of this study. Initial and final visual acuity, indications for PK, surgical procedure, postoperative therapy, complications, total number of repeat PKs, length of follow-up, and the final outcome were recorded. RESULTS Thirty-two PKs were performed in 16 eyes of 13 patients with advanced OCP (6 patients), OCP as a sequela of Stevens-Johnson syndrome (2 patients), Stevens-Johnson syndrome (3 patients), and toxic epidermal necrolysis (2 patients). The indications for the first PK were corneal perforation in six eyes (37.5%) and extensive corneal scarring in ten eyes (62.5%). Preoperative visual acuity was counting fingers in five eyes, hand motions in eight, and light perception in three. Preoperative therapy included systemic chemotherapy (8 patients), mucous membrane grafting (9 eyes), lamellar keratoplasty (2 eyes), superficial keratectomy (1 eye), and corneal dye laser photocoagulation (6 eyes). The mean follow-up period was 4.6 years (3 months-13 years). Eight eyes (50%) had clear grafts, and three eyes (18.7%) had 20/200 or better visual acuity at last visit. The major causes of graft failure were epithelial defect formation/persistence, stromal ulceration, perforation, and graft rejection. CONCLUSIONS These results indicate that PK may be performed for tectonic reasons, but prospects for restoration of sight in patients with advanced cicatrizing conjunctival diseases, even after extensive preoperative medical and surgical therapy, are limited.

Posterior Segment Ocular Manifestations in Patients with HLA-B27—associated Uveitis

PURPOSE To describe a series of patients with seronegative arthritic syndromes and HLA-B27-associated uveitis with severe, sight-threatening, posterior segment ocular manifestations. METHODS The authors reviewed the records of 29 patients (17.4%) with posterior segment involvement from a cohort of 166 patients with HLA-B27-associated uveitis. The inclusion criteria included individuals with a positive HLA-B27 who had at least one of the following findings: (1) severe vitreous inflammation; (2) papillitis; (3) retinal vasculopathy; or (4) pars plana exudates. The study population comprised 13 men and 16 women with a mean age at onset of uveitis of 35.2 years. The average duration of the uveitis was 5.3 years, and the median follow-up time was 26 months. FINDINGS Posterior segment involvement occurred in 34 eyes of the 29 patients. The most common findings included severe and diffuse vitritis in 93.1% of the patients and papillitis in 24 patients (82.7%). Retinal vasculitis occurred in seven patients (24.1%), and pars plana exudates were present in two patients (6.8%). Cystoid macular edema (37.9%) and epiretinal membrane (17.2%) were common causes of visual impairment. Systemic immunosuppressive therapy was required for control of inflammation in 32% of the patients. CONCLUSION HLA-B27-associated uveitis may be related to severe, sight-threatening posterior segment manifestations in some patients; this is an under-recognized phenomenon. These patients may require the use of aggressive systemic immunosuppressive therapy to control inflammation and preserve vision.

Fibrin glue versus sutures for conjunctival autografting in pterygium surgery: a prospective comparative study

Aim: To compare the use of fibrin glue versus sutures for fixating conjunctival autografts in patients undergoing pterygium excision. Methods: Fifty patients (50 eyes) with primary pterygium were randomised to undergo pterygium surgery using either fibrin glue (25 eyes) or 8-0 Vicryl sutures (25 eyes) to attach the conjunctival autograft. The patients were followed up for 12 months. Outcome measures were postoperative patient comfort, duration of surgery and recurrence of pterygium. Results: In the fibrin glue group, the mean operation time was 15.7 (SD 2.4) min (range 12–18 min) and in the suture group (p<0.001) it was 32.5 (6.7) min (range 25–40 min). The intensity of the postoperative pain, foreign-body sensation, irritation and epiphora were significantly lower in the fibrin glue group than in the suture group (p<0.001). The intensity of itchy sensation at the first two postoperative visits was lower among patients in the fibrin glue group (five patients, 20%) than in the suture group (12 patients, 48%) (p<0.05). Two patients in the fibrin glue group had partial graft dehiscence; these grafts were successfully reattached with fibrin glue. At the end of follow-up, pterygium recurrence was observed in one eye (4%) in the fibrin glue group and in three eyes (12%) in the suture group (p<0.05). Conclusion: The use of fibrin glue in pterygium surgery with conjunctival autografting significantly reduces surgery time, improves postoperative patient comfort and results in a lower recurrence rate compared with suturing.

Microbial keratitis following penetrating keratoplasty

PURPOSE To investigate the prevalence of microbial keratitis, predisposing risk factors and treatment modalities in patients who developed keratitis following penetrating keratoplasty (PK). PATIENTS AND METHODS The records of 285 patients who had undergone PK between January 1991 and December 1995 in a tertiary care center were reviewed. Patients who developed postoperative microbial keratitis were evaluated for predisposing risk factors, microbiological etiology, response to broad spectrum antibiotic therapy and subsequent PK. Patients were mainly treated with fortified topical antibiotics with or without repeat PK. RESULTS Of the 285 patient records reviewed, microbial keratitis developed in 21 eyes of 21 patients (7.4%). Seventy-one percent of infections occurred within 6 months after grafting. Keratitis initially began from the donor-recipient border in 16 cases (76.2%) and were central or paracentral in 5 patients. Predisposing risk factors included loose or exposed suture (9), suture removal (1), persistent epithelial defect (3), graft failure (3), contact lens wear (1), Stevens-Johnson syndrome (1). Fifteen (71.4%) patients were culture-positive consisting of Streptococcus pneumoniae (7), Staphylococcus aureus (5), Pseudomonas aureginosa (2), and Hemophilus influenzae (1). Forty-three percent of patients were successfully treated with medical therapy only. Seven patients underwent second PK for visual rehabilitation and 4 for tectonic purposes. After medical and surgical therapy, graft clarity was achieved in 17 (81%) of patients. CONCLUSIONS The microbial keratitis following PK is a major postoperative problem affecting the long term prognosis. Careful selection of patients, and preoperative and postoperative control of risk factors, may decrease the frequency of this complication. Several factors, including loose or exposed sutures, epithelial defects, ocular surface disorders, and graft failure, may predispose patients to develop microbial keratitis following PK.

Comparison of conjunctival autograft with amniotic membrane transplantation for pterygium surgery: surgical and cosmetic outcome.

Purpose: To compare the clinical results of conjunctival autograft and amniotic membrane transplantation (AMT) for primary and recurrent pterygium excision. In an effort to determine whether AMT yields acceptable cosmetic results as conjunctival autografting in pterygium surgery, we compared the final cosmetic outcomes of these 2 techniques. Methods: We performed a prospective, randomized clinical study of 78 eyes (78 patients) divided into 2 groups. Forty eyes (28 with primary and 12 with recurrent pterygia) received conjunctival limbal autograft (group 1), and 38 eyes (27 with primary and 11 with recurrent pterygia) received AMT (group 2) after extensive removal of pterygium. Mean follow-up time was 16.6 ± 3.52 months in group 1 and 13.4 ± 2.08 months in group 2. The results were evaluated by clinical examination and photographing and final appearances were graded from 1 to 4. Grade 4 represented true recurrence, whereas grade 3 indicated unacceptable cosmetic appearance. Results: Recurrence rates of primary, recurrent, and all pterygia in group 1 and group 2 were 3.6%, 16.7%, and 7.5% and 3.7%, 18.2%, and 7.9%, respectively. There was no significant difference in recurrence rates between the 2 groups (P = 1.00 for all). The rates of final appearance as grade 3 were 10.0% in group 1 and 21.1% in group 2, and the difference was statistically significant (P = 0.048). No major complications occurred during the follow-up period. Conclusions: Although better results in the final appearance were achieved using conjunctival autografting than with AMT, AMT can be a useful alternative in pterygium surgery, especially in those patients who may have a limited amount of conjunctiva for future surgeries.

Revisiting the vicious circle of dry eye disease: a focus on the pathophysiology of meibomian gland dysfunction

Meibomian gland dysfunction (MGD) is the most frequent cause of dry eye disease (DED). Eyelid inflammation, microbial growth, associated skin disorders as well as potentially severe corneal complications culminate to make MGD a complex multifactorial disorder. It is probable that MGD is a heterogeneous condition arising from any combination of the following five separate pathophysiological mechanisms: eyelid inflammation, conjunctival inflammation, corneal damage, microbiological changes and DED resulting from tear film instability. The pathogenesis of both MGD and DED can be described in terms of a ‘vicious circle’: the underlying pathophysiological mechanisms of DED and MGD interact, resulting in a double vicious circle. The MGD vicious circle is self-stimulated by microbiological changes, which results in increased melting temperature of meibum and subsequent meibomian gland blockage, reinforcing the vicious circle of MGD. Meibomian gland blockage, dropout and inflammation directly link the two vicious circles. MGD-associated tear film instability provides an entry point into the vicious circle of DED and leads to hyperosmolarity and inflammation, which are both a cause and consequence of DED. Here we propose a new pathophysiological scheme for MGD in order to better identify the pathological mechanisms involved and to allow more efficient targeting of therapeutics. Through better understanding of this scheme, MGD may gain true disease status rather than being viewed as a mere dysfunction.

Effect on Astigmatism of the Location of Clear Corneal Incision in Phacoemulsification of Cataract

PURPOSE To investigate the refractive results of clear corneal incision performed at the steepest meridian of pre-existing corneal astigmatism. METHODS One hundred eighty-two patients with astigmatism > 0.75 diopters (D) were evaluated. Superior, temporal, nasal, superotemporal, or superonasal clear corneal incisions were performed at the steep meridian. Refraction, visual acuity, and topography values were evaluated, and changes in surgically induced astigmatism were calculated by vector analysis using the Fourier formula. Paired t test was used to compare mean values. RESULTS Postoperative cylinder values showed minor changes in all groups, except the nasal group. Nasal incision increased preoperative cylinder from 1.13 D to 1.83 D 6 months after surgery. Temporal and superotemporal incisions resulted only in small astigmatic changes. Conversely, superior, superonasal, and nasal incisions induced more pronounced astigmatism. CONCLUSIONS Performing clear corneal incision for phacoemulsification of cataract at the steep meridian resulted in small changes with temporal incisions, whereas nasal incisions resulted in higher surgically induced astigmatism.

Cataract surgery in patients with sarcoidosis-associated uveitis

PURPOSE The authors analyzed the incidence of cataract development and the visual outcome of cataract surgery performed on patients with sarcoidosis-associated uveitis who were treated at the Immunology Service at the Massachusetts Eye and Ear Infirmary during a 17-year period. METHODS The records of 102 patients with sarcoidosis-associated uveitis who were treated with topical and regional corticosteroids, systemic nonsteroidal anti-inflammatory drugs, systemic steroids, or with systemic immunosuppressive chemotherapy were reviewed. Cataract surgery was performed on those eyes in which cataract developed, resulting in decreased visual acuity of 20/100 or less. The incidence of cataract development and visual results of cataract extraction and intraocular lens implantation were analyzed. RESULTS In this cohort of 102 patients, visually significant cataracts that warranted surgery developed in 10 (16 eyes). In addition, four patients (5 eyes) had a visually significant cataract at the time of first evaluation. A total of 14 patients (21 eyes) underwent cataract surgery. Posterior chamber lens implantation accompanied cataract surgery in 19 (90.5%) of 21 eyes. The average final visual acuity of the 21 eyes after cataract surgery was 20/51, and 61% of the eyes achieved a stable visual acuity of 20/40 or better. The major causes of the decreased visual acuity in patients who had less than 20/40 visual acuity were sequelae of chronic posterior uveitis, cystoid macular edema, epiretinal membrane, and glaucomatous optic nerve damage. CONCLUSION Posterior chamber lens implantation and cataract surgery in patients with sarcoidosis-associated uveitis can be well tolerated when absolute control of the inflammation is achieved. Pre-existing retinal pathology and glaucoma as a result of uncontrolled inflammation resulting in permanent ocular structural damage were found to be the most important factors for determining the postoperative final visual acuity.

Ocular surface changes in keratoconjunctivitis sicca with silicone punctum plug occlusion

Purpose. To evaluate histopathologic and clinical response to silicone plug insertion in dry eye patients. Methods. Punctal plugs were placed in 32 eyes of 18 dry eye patients with aqueous deficiency who were on maximum medical therapy and who had Schirmer testing with topical anesthetic measuring less than 5 mm. Pre-treatment and posttreatment (6 weeks and 1 year) evaluations included temporal and inferior quadrant impression cytology examinations, Schirmer-1, BUT, corneal fluorescein and rose-bengal staining patterns and questionnaire scores. The cytology samples were graded according to the method described by Nelson. Results. There was an improvement in subjective symptoms of patients 6 weeks after punctal occlusion. Corneal fluorescein and rose-bengal staining scores decreased from a mean of 5.33 ± 1.74 to 1.37 ± 1.48 and from 5.90 ± 1.2 to 2.45 ± 1.89 (p < 0.05) respectively. BUT values increased from 2.98 ± 1.1 to 11.3 ± 3.1 seconds (p < 0.05) at 6 weeks posttreatment. Increase in goblet cell density was observed after punctal occlusion at 6 weeks (p < 0.05) and at 1 year (p < 0.05) compared to the pre-treatment values. After occlusion, 3% of temporal specimens had Grade 0 squamous metaplasia, 63% had Grade 1, 34% had Grade 2; while 25% of inferior specimens had Grade 0, 56% had Grade 1, 19% had Grade 2 squamous metaplasia. Conclusions. Punctum plug occlusion in keratoconjunctivitis sicca provides improvement of tear film stability, ocular surface staining scores, conjunctival squamous metaplasia grades and goblet cell density. Increased ocular surface exposure to essential tear components with punctal occlusion may be important for the genesis of these changes.