Eiki Goto

Treatment of dry eye by autologous serum application in Sjögren’s syndrome

AIM To evaluate the efficacy of autologous serum application for the treatment of dry eye in Sjögren’s syndrome. METHODS The stability of essential components (EGF, vitamin A, and TGF-β) in preserved serum were examined following preservation at 4°C and −20°C. In a primary clinical trial, 12 patients with Sjögren’s syndrome were treated with autologous serum (diluted to 20% with sterile saline) for 4 weeks, and vital staining of the ocular surface was compared before and after treatment. The effects of serum on mucin (MUC-1) expression were observed in cultured conjunctival epithelial cells in vitro. RESULTS EGF, vitamin A, and TGF-β were well preserved for up to 1 month in the refrigerator at 4°C and up to 3 months in the freezer at −20°C. Rose bengal and fluorescein scores improved significantly from the initial scores of 5.3 and 5.6 to 1.7 and 2.5 after 4 weeks, respectively. The additive effect of human serum for cultured conjunctival epithelial cells showed significant MUC-1 upregulation on the cell surface. CONCLUSION Autologous serum application is a safe and efficient way to provide essential components to the ocular surface in the treatment of dry eye associated with Sjögren’s syndrome.

Treatment of persistent corneal epithelial defect by autologous serum application

OBJECTIVE To evaluate the efficacy of autologous serum application for the treatment of persistent epithelial defect. DESIGN Prospective, clinical, noncomparative case series. PARTICIPANTS A total of 16 eyes were studied. INTERVENTION Autologous serum was prepared from the patients and diluted to 20% by saline. The patients were instructed to use the autologous serum six to ten times a day. The concentration of vitamin A, epidermal growth factor (EGF), and transforming growth factor-beta (TGF-beta) was measured at 1 week and 1 month stored in the refrigerator and 1 month and 3 months in the freezer. MAIN OUTCOME MEASURES Time to closure of epithelial defect. RESULTS Vitamin A, EGF, and TGF-beta were stable during the 1 month in the refrigerator and 3 months in the freezer. Among 16 persistent epithelial defects, 7 (43.8%) healed within 2 weeks, 3 (18.8%) healed within 1 month, and the remaining 6 (37.5%) did not respond within 1 month. No apparent side effect of autologous serum application was observed. CONCLUSIONS Autologous serum application healed 43.8% of persistent defect within 2 weeks and 62.5% within 1 month.

TRANSPLANTATION OF HUMAN LIMBAL EPITHELIUM CULTIVATED ON AMNIOTIC MEMBRANE FOR THE TREATMENT OF SEVERE OCULAR SURFACE DISORDERS

PURPOSE To study the short-term clinical results of transplanting of cultivated corneal/limbal epithelial cells on human amniotic membrane (AM) for limbal deficiency. DESIGN Noncomparative, retrospective interventional case series. PARTICIPANTS Thirteen eyes of 13 patients with severe limbal deficiency (Stevens-Johnson syndrome in eight eyes, ocular cicatricial pemphigoid in three eyes, and chemical burns in two eyes) were treated at the department of Ophthalmology, Tokyo Dental College, Japan. INTERVENTION Cultivated allo-limbal epithelium was transplanted onto the ocular surface of patients with severe limbal deficiency. MAIN OUTCOME MEASURES Ocular surface reconstruction with corneal epithelialization, changes in visual acuity, and postoperative complications were studied. Histologic examinations were also performed on cultivated epithelium. RESULTS Cultivated corneal epithelium on AM formed two to three layers with the formation of basement membrane-like structures. After the surgery, the epithelium regenerated and covered the ocular surface in eight eyes (61.5%). However, three of the eight eyes developed partial conjunctival invasion, and two eyes later developed epithelial defects. At last examination, corneal epithelialization was achieved in six eyes (46.2%). Five eyes had conjunctivalization, one eye had dermal epithelialization, and one eye was not epithelialized. Complications were corneal perforation in four eyes and infectious keratitis in two eyes. CONCLUSIONS This study demonstrates that the success rate for transplanting cultivated allo-limbal epithelium on the AM is not different from the conventional limbal and AM transplantation for the treatment of severe limbal stem cell dysfunction.

The International Workshop on Meibomian Gland Dysfunction: Report of the Subcommittee on Management and Treatment of Meibomian Gland Dysfunction

The goals of the subcommittee were to review the current practice and published evidence of medical and surgical treatment options for meibomian gland dysfunction (MGD) and to identify areas with conflicting, or lack of, evidence, observations, concepts, or even mechanisms where further research is required. To achieve these goals, a comprehensive review of clinical textbooks and the scientific literature was performed and the quality of published evidence graded according to an agreed on standard, using objective criteria for clinical and basic research studies adapted from the American Academy of Ophthalmology Practice Guidelines1 (Table 1). It should be noted that, in many of the clinical textbooks and previous reports, terminology is often interchanged and the management of anterior and posterior blepharitis and/or meibomitis is often considered concurrently. Thus, a broad scope of documents was reviewed in this process. Consistency in terminology and global adoption of the term “meibomian gland dysfunction” would significantly aid clinical research and clinical care in MGD going forward. Table 1. Grading Level of Evidence of Clinical and Basic Research Studies1

Meibomian gland dysfunction in patients with Sjögren syndrome

OBJECTIVE Changes in the ocular surface of patients with Sjögren syndrome (SS) often are more severe than those in patients with dry eye without SS. This study was conducted to investigate the possible involvement of meibomian gland dysfunction in SS-related ocular surface abnormalities. DESIGN A nonrandomized, prospective, clinical study. PARTICIPANTS Twenty-seven eyes of 27 consecutive patients with SS (SS group) were studied. Twenty-nine eyes of age- and gender-matched non-SS patients with aqueous tear deficiency (non-SS group) were examined as control subjects. INTERVENTION Changes in the ocular surface, tear function, and meibomian gland were examined. MAIN OUTCOME MEASURES Tear evaporation rate, meibomian gland expression, and meibography were measured. RESULTS Fluorescein and rose bengal staining scores were significantly higher in the SS group than in the non-SS group (P = 0.0001). Evaporation of tears was increased significantly in the SS group compared with the non-SS group. There were no significant differences in the rate of tear production between the SS and non-SS groups. Meibography showed that 11 (57.9%) of 19 eyes in the SS group had gland dropout (i.e., histologic destruction of meibomian glands) in more than half of the tarsus. The incidence was significantly higher than that in the non-SS group (5 [18.5%] of 27 eyes; P = 0.005). CONCLUSIONS The results of this study indicate that destruction of meibomian glands and an increase in tear evaporation often are associated with changes in the ocular surface in patients with SS. Severe ocular surface changes in patients with SS may be attributed, in part, to the meibomian gland dysfunction.

Abnormal protein profiles in tears with dry eye syndrome

PURPOSE To verify the hypothesis that protein concentrations, such as lactoferrin, epidermal growth factor (EGF), and aquaporin 5 (AQP5), in tears are abnormal in patients with dry eye. DESIGN Prospective case-control study. METHODS One hundred three dry eye patients were divided into three groups: dry eye not associated with the Sjögren syndrome (non-SS; n = 71), Sjögren syndrome (SS; n = 23), and Stevens-Johnson syndrome (SJS; n = 9). Sixteen normal control subjects were also checked. The concentrations of lactoerrin, EGF, and AQP5 were measured by enzyme-linked immunosorbent assay. RESULTS The concentration of lactoferrin was significantly decreased in tears of non-SS (P =.0001), SS (P =.00005), and SJS (P =.0006) patients compared with control subjects. The concentration of EGF was significantly decreased in non-SS (P =.0005), SS (P =.00002), and SJS (P =.0001) patients compared with control subjects. The concentration of AQP5 was significantly increased in tears of only SS patients (P =.01) compared with control subjects and increased in tears of only SS patients compared with non-SS patients (P =.007). CONCLUSIONS The decrease in both lactoferrin and EGF was found not only in SS patients but also in non-SS patients, indicating that tear components in dry eyes differ in their quantity and quality. Quantification of AQP5 increased only in SS patients, suggesting that AQP5 protein leaks into the tears when acinar cells of the lacrimal gland are damaged by lymphocytic infiltration.

The challenge of dry eye diagnosis

The currently available methods for the diagnosis of dry eye are still far from being perfect for a variety of reasons. This review attempts to highlight the advantages and disadvantages of both traditional tests (such as Schirmer’s test, break-up time and ocular surface staining) and innovative noninvasive procedures, including tear meniscus height measurement, corneal topography, functional visual acuity, tear interferometry, tear evaporimetry and tear osmolarity assessment.

Treatment of superior limbic keratoconjunctivitis by application of autologous serum.

Purpose. To determine the efficacy of autologous serum drops in the treatment of superior limbic keratoconjunctivitis (SLK). Methods. Twenty-two eyes of 11 patients were diagnosed with SLK. All eyes were treated with 20% diluted autologous serum eyedrops 10 times a day in addition to ongoing treatment of dry eye. Fluorescein and rose bengal staining scores, as well as subjective symptom gradings, were performed before and after 4 weeks of therapy. Results. Nine of the 11 patients responded well to treatment (82%). The average rose bengal and fluorescein score improved (p < 0.05), and there was subjective improvement. Conclusion. Autologous serum application can be used as an alternative mode of therapy in SLK.

Treatment of non-inflamed obstructive meibomian gland dysfunction by an infrared warm compression device

Aim: To test the short term efficacy and safety of an infrared warm compression device (IWCD, Eye Hot, Cept Co, Tokyo, Japan) as treatment for non-inflamed meibomian gland dysfunction (MGD). Methods: 37 subjects with non-inflamed obstructive MGD, with and without aqueous tear deficiency (ATD) dry eye, participated in a prospective non-comparative interventional case series. Symptom scores, face scores, tear evaporation rates, fluorescein and rose bengal vital staining, tear break up time (BUT), Schirmer test, meibomian gland obstruction, and meibography were compared before and after 2 weeks of therapy. Results: In a total of 37 cases, total subjective symptom scores and subjective face scores improved significantly, from 12.3 (SD 5.9) to 8.4 (6.1), and from 7.0 (1.7) to 5.3 (2.0) (both p <0.0001). The results for tear evaporation rates during forced blinking (p = 0.002), fluorescein staining (p = 0.03), rose bengal staining (p = 0.03), BUT (p <0.0001), and meibomian gland orifice obstruction score (p <0.0001) had also improved significantly at the end of the 2 week period of infrared thermotherapy. No complaints and/or complications of the IWCD were reported. Conclusion: The IWCD was effective and safe for the treatment of MGD. Improved tear stability associated with release of meibum is a possible mechanism of this treatment.

The features of dry eye disease in a Japanese elderly population.

Purpose. The purpose of this study is to assess the features of dry eye disease in a Japanese elderly population. Methods. One hundred thirteen left eyes of 113 pensioners (50 males, 63 females; mean age, 67.5 ± 5.7 years) aged over 60 years were recruited in this study. The subjects underwent careful slit-lamp examinations of the conjunctiva, ocular surface, and the eye lids. Tear film breakup time (BUT) examinations, Schirmer test-I, and fluorescein staining of the ocular surface and transillumination of the eyelids were also performed. Dry eye symptomatology was assessed with a symptom questionnaire. Japanese Dry Eye Diagnostic Criteria were used in this study. Results. Ocular tiredness, irritation, dryness, and foreign body sensation were the most frequently reported symptoms by the patients. A total of 73.5% of the eyes had definite dry eyes. A total of 39.8% of the eyes had a Schirmer test reading <5 mm. Mean Schirmer test value was 9.4 ± 7.8 mm. The mean BUT score was 4.0 ± 2.8 seconds. A total of 76.9% of the eyes had positive fluorescein staining of the cornea. Meibomian gland dysfunction and conjunctivochalasis were found as frequent factors in relation to dry eye disease with meibomian grand dropout showing positive correlation with tear instability. Conclusion. Qualitative and quantitative disorders of the tear film were far more common than recognized in this population of elderly subjects, meibomian gland dysfunction being the most common associate of the tear film disorder and dry eye status. Conjunctivochalasis (conjunctival laxity), although commonly associated with dry eye disease in the elderly, was observed not to be related to age or gender in this study.