Minako Kaido

Treatment of severe ocular-surface disorders with corneal epithelial stem-cell transplantation.

BACKGROUND Conditions that destroy the limbal area of the peripheral cornea, such as the Stevens-Johnson syndrome, ocular pemphigoid, and chemical and thermal injuries, can deplete stem cells of the corneal epithelium. The result is scarring and opacification of the normally clear cornea. Standard corneal transplantation cannot treat this form of functional blindness. METHODS We performed and evaluated 70 transplantations of corneal epithelial stem cells from cadaveric eyes into 43 eyes of 39 patients with severe ocular-surface disorders and limbal dysfunction. Medical treatment had failed in all patients. The patients had a mean preoperative visual acuity of 0.004 (only being able to count the number of fingers presented by the examiner) in the affected eyes, which satisfies the criteria for legal blindness in most countries. In 28 eyes, we also performed standard corneal transplantation. Stem-cell transplantations were performed as many as four times on 1 eye if the initial results were not satisfactory; 19 eyes had multiple transplantations. Patients were followed for at least one year after transplantation. RESULTS A mean of 1163 days after stem-cell transplantation, 22 of the 43 eyes (51 percent) had corneal epithelialization; of the 22 eyes, 7 eyes had corneal stromal edema and 15 eyes had clear corneas. Mean visual acuity improved from 0.004 to 0.02 (vision sufficient to distinguish the largest symbol on the visual-acuity chart from a distance of 1 m) (P<0.001). The 15 eyes in which the cornea remained clear had a final mean visual acuity of 0.11 (the ability to distinguish the largest symbol from a distance of 5 m). Complications of the first transplantation included persistent defects in the corneal epithelium in 26 eyes, ocular hypertension in 16 eyes, and rejection of the corneal graft in 13 of 28 eyes. The epithelial defects eventually healed in all but two of the eyes. CONCLUSIONS Transplantation of corneal epithelial stem cells can restore useful vision in some patients with severe ocular-surface disorders.

A new surgical technique for deep lamellar keratoplasty with single running suture adjustment

PURPOSE To improve the technique of deep lamellar keratoplasty. METHODS For the recipient eye, a divide-and-conquer technique was applied to deep lamellar keratoplasty. After trephinization, the recipient cornea within the trephine was divided into four quadrants to facilitate lamellar dissection at approximately 70% depth. This procedure of division was continued until the Descemet membrane was exposed in the central area. The corneal graft was placed with an adjusted single running suture. Seventeen eyes were treated with this technique. RESULTS In 17 eyes of 15 patients, the mean visual acuity 6 months or more after deep lamellar keratoplasty was 20/52 with eyeglass correction and 20/80 without eyeglass correction. At 6 months or more after deep lamellar keratoplasty, the mean +/- SD keratometric astigmatism in 17 eyes was 3.2 +/- 2.3 diopters. CONCLUSION This technique facilitates deep lamellar keratoplasty and prevents high or excessive astigmatism after surgery.

Improved functional visual acuity after punctal occlusion in dry eye patients.

PURPOSE To report an increased functional visual acuity, which was recently reported as a simulation of visual function of daily acts of gazing, in dry eye patients after punctal occlusion. DESIGN Prospective comparative interventional study. METHODS We measured ordinary best-corrected visual acuity and functional visual acuity in eight eyes of eight dry eye patients after punctal occlusion, and compared the results with those of 22 eyes of 22 dry eye patients without punctal occlusion. RESULTS Functional visual acuity in dry eye patients after punctal occlusion was 0.962 in decimal notation, which was significantly higher than that of patients without punctal occlusion, 0.283 (P <.0001). CONCLUSIONS This study shows that punctal occlusion can improve the impaired functional visual acuity of dry eye patients.

Evaluation of lipid oxidative stress status in Sjögren syndrome patients

PURPOSE We evaluated the levels of lipid oxidative stress markers and inflammatory cells from tears and conjunctiva of patients with Sjögren syndrome (SS) and normal subjects. METHODS We examined 31 eyes of 16 patients (16 females) with SS and 15 eyes of 10 healthy controls (2 males and 8 females) in this prospective study. All subjects underwent a Schirmer test, measurement of tear film break-up time, vital stainings, confocal microscopy of the conjunctiva, tear collection for hexanoyl-lysine (HEL), ELISA, and conjunctival brush cytology. Brush cytology samples underwent immunohistochemistry (IHC) staining with HEL and 4-hydroxy-2-nonenal (4HNE). Hematoxylin-eosin and IHC staining with HEL and 4HNE also were performed on conjunctival samples of SS patients and controls. RESULTS The tear stability and vital staining scores were significantly worse in eyes of SS patients compared to the controls. Conjunctival inflammatory cell density was significantly higher in SS subjects compared to controls. The numbers of conjunctival cells stained positively for HEL and 4HNE were significantly higher in SS patients compared to controls. Tear HEL concentrations correlated significantly with staining scores and inflammatory cell density in confocal microscopy. Conjunctival specimens also revealed higher numbers of cells stained positively for inflammatory markers, as well as HEL and 4HNE in the IHC stainings. CONCLUSIONS Increase of the oxidative stress status in the conjunctiva of SS patients appears to have a role in the pathogenesis of dry eye disease. A close relationship may exist between reactive oxygen species (ROS) production, lipid peroxidation related membrane damage, and inflammatory processes in dry eye.

Corneal Fluorescein Staining Correlates with Visual Function in Dry Eye Patients

PURPOSE To investigate the changes in functional visual acuity (VA) and higher order aberrations in dry eye patients. METHODS In this prospective comparative case series, 22 right eyes were classified into those with or without superficial punctate keratopathy (SPK) in the central cornea of 22 patients with Sjögren syndrome; 10 right eyes of 10 normal subjects served as the control. Serial measurements of VAs using a functional VA measurement system and higher order aberrations using a wavefront sensor were performed under blink-free conditions without topical anesthesia over a 10-second period. The parameters for each measurement were compared among the SPK-positive and -negative and normal groups. The correlation between those parameters was also analyzed. RESULTS Dry eye with SPK showed significant deterioration of visual function and optical quality compared with dry eye without SPK and in normal eyes, as detected by both the visual maintenance ratio (VMR; P < 0.05) and the variation of VA (P < 0.05) and by comalike and total higher order aberrations (P < 0.05). Moreover, the severity of epithelial damage at the central cornea correlated significantly with VMR (P < 0.01) and variation of VA (P < 0.01) as well as comalike (P < 0.05) and total higher order aberrations (P < 0.05). The dry eye group without SPK showed minor visual deterioration compared with normal eyes, as detected only by VMR (P < 0.05). CONCLUSIONS Optical disturbances at the central optical zone of the cornea in dry eye disease may affect visual performance. Functional VA measurement may be an applicable method of evaluating visual performance in dry eyes that is as efficient as wavefront aberration measurements.

Conjunctival in vivo confocal scanning laser microscopy in patients with sjögren syndrome

PURPOSE To demonstrate the conjunctival alterations in patients with Sjögrens (SSDE) and non-Sjögrens syndrome dry eye (NSSDE) using a new generation confocal microscope (HRTII/ RCM; Heidelberg Engineering, Heidelberg, Germany), in a prospective controlled study. METHODS Twenty-eight right eyes of 28 patients with SSDE (28 women; mean age, 58.2 +/- 14.3 years), 7 right eyes of patients with NSSDE (7 women; mean age, 66.1 +/- 14.4 years), and 14 right eyes of 14 age- and sex-matched control subjects were studied. All subjects underwent the Schirmer test, tear film breakup time (BUT), vital staining, and confocal microscopy of the temporal bulbar conjunctiva. The density of conjunctival epithelial cells, epithelial microcysts, and conjunctival and corneal inflammatory infiltrates were also assessed. RESULTS The tear quantity, stability, and vital staining scores were significantly worse in patients with SSDE or NSSDE than in control subjects (P < 0.001 and P < 0.05, respectively). Eyes of the patients with SSDE or NSSDE had a significantly higher density of conjunctival and corneal inflammatory infiltrates than did the control eyes (P < 0.001). Conjunctival inflammatory cell densities showed a negative correlation with tear stability and tear quantity and a positive correlation with the vital staining scores. Conjunctival epithelial cell densities were significantly lower in SSDE and NSSDE compared with control subjects (P < 0.05). The density of epithelial cysts was significantly higher in SS than in healthy control eyes (P < 0.001). CONCLUSIONS Confocal scanning laser microscopy was an efficient and a noninvasive tool for the quantitative assessment of the conjunctival inflammation and epithelial cell densities as well as evaluation of conjunctival morphologic alterations, such as microcysts in patients with SSDE and NSSDE dry eye disease.

Efficacy of punctum plug treatment in short break-up time dry eye.

Purpose. To evaluate the efficacy of punctum plug insertion on tear and dynamic visual function in dry eye patients with short break-up time (s-BUT) of the tears. Methods. A prospective comparative case series design was used. Twenty-seven eyes of 27 dry eye patients with a s-BUT seen at Keio University School of Medicine, Department of Ophthalmology, were studied. Functional visual acuity (FVA) measurements, tear function examinations and ocular surface evaluations including Schirmer test, tear break-up time, fluorescein and Rose Bengal vital staining scores were performed before and 1 month after insertion of punctum plugs (PP) in dry eye patients with s-BUT. Degree of satisfaction with the PP treatment was also graded. Results. Nineteen out of 27 eyes (70.4%) showed a satisfactory outcome with the PP treatment because of decreased subjective dry eye symptoms. On the other hand, six out of eight eyes with an unsatisfactory outcome had epiphora. The visual maintenance ratio value was observed to significantly increase from 0.87 ± 0.09 to 0.91 ± 0.07 in eyes with no epiphora, whereas the visual maintenance ratio value significantly decreased from 0.98 ± 0.10 to 0.86 ± 0.13 in the group of eyes with epiphora after PP treatment. (p < 0.05) Likewise, FVA significantly improved after PP insertion in the group with no epiphora and decreased in eyes with epiphora. Visual acuity in the conventional Landolt visual testing remained significantly unchanged in both group of eyes with or without epiphora. Conclusions. FVA was useful in assessing and quantifying vision related symptomatology in s-BUT type of dry eye treated with PP occlusion.

Diseases associated with ocular surface abnormalities: the importance of reflex tearing.

AIM To investigate the correlation between tear function tests and ocular surface integrity in patients with dry eye. METHODS 297 dry eye patients (55 Sjögren’s syndrome, two male and 53 female, average age 52.4 (SD 15.0) years, and 242 non-Sjögren’s syndrome, 41 male and 201 female, average age 53.5 (14.1) years) were examined. The following tear function tests were performed: (1) cotton thread test, (2) Schirmer test with topical anaesthesia, (3) Schirmer test without anaesthesia, (4) Schirmer test with nasal stimulation, (5) tear clearance test, and (6) tear break up time (BUT). The ocular surface was evaluated by rose bengal and fluorescein staining. Correlation analysis was performed between each tear function index and vital staining scores. RESULTS Among the six tear function tests, the Schirmer test with nasal stimulation correlated most with both of the vital stains (ρ=0.530 for rose bengal and 0.393 for fluorescein). The Schirmer test with or without anaesthesia correlated slightly with rose bengal staining, whereas tear clearance test and tear break up time slightly correlated with fluorescein staining. CONCLUSION Vital staining of the ocular surface correlates most with reflex tearing measured by the Schirmer test with nasal stimulation.

Effects of Diquafosol Tetrasodium Administration on Visual Function in Short Break-Up Time Dry Eye

PURPOSE To investigate the effect of diquafosol tetrasodium on tear and visual function in short break-up time (sBUT) dry eye (DE). METHODS This interventional nonrandomized comparative study involved 11 eyes in 11 patients with sBUT DE (symptom-positive sBUT group) and 13 eyes in 13 volunteers with BUT values ≤5 s without DE symptoms (symptom-negative sBUT group). Tear function was assessed by measuring BUT and Schirmer values. Serial measurements were made of visual acuities (using a functional visual acuity measurement system) and higher-order aberrations (using a wavefront sensor). The parameters were compared before and 1 month after diquafosol tetrasodium instillation. Any changes in symptomatology after administration were also recorded. RESULTS After diquafosol tetrasodium administration, BUT values tended to increase in the symptom-positive sBUT group (P=0.07) and significantly increased in the symptom-negative sBUT group (P<0.05). LogMAR functional, minimal, and maximal visual acuities and higher-order aberrations significantly decreased after diquafosol tetrasodium administration in the symptom-positive sBUT group (P<0.05), while there were no significant changes in these values in the symptom-negative sBUT group (P>0.05). Diquafosol tetrasodium administration provided relief of DE symptoms in 75% of patients in the symptom-positive sBUT group. CONCLUSIONS Diquafosol tetrasodium appeared to improve tear film stability and visual function in sBUT DE.

Optical aberrations and visual disturbances associated with dry eye

Optical aberrations and visual disturbances are associated with dry eye, although visual impairment is often not detected by conventional visual acuity testing. The newly developed functional visual acuity (FVA) device allows continuous dynamic evaluation of distance visual acuity and assessment of the effect of natural tear film status on dynamic visual function. Similarly, to detect corneal surface irregularities during sustained eye opening in dry eye subjects, a new tear stability analysis system (TSAS) has been developed. Both FVA and TSAS measurement systems seem to be effective tools in the assessment of dynamic visual acuity changes in dry eye and normal subjects. Both methods were also found to be helpful in the evaluation of the outcome of management of dry eye disease. FVA testing has been suggested to be an important indication of an individuals performance in relation to certain daily activities, such as driving, reading and working at a video display terminal. This review provides illustrations of results obtained from FVA and TSAS systems.