Cataract surgery in patients with advanced Mooren's ulcer.

BACKGROUND: We describe 2 patients with severe Mooren's ulcer who underwent phacoemulsification and intraocular lens implantation surgery. The clinical features of this disease are highlighted. CASE: A detailed study of the ocular and laboratory findings in these patients, together with a review of the literature, is presented. OBSERVATIONS: There was a visually rewarding outcome after phacoemulsification and intraocular lens implantation were performed, and Mooren's ulcer did not recur. CONCLUSION: We conclude that phacoemulsification-aspiration and intraocular lens implantation surgery with a small incision can be successfully performed in patients with Mooren's ulcer after complete control of inflammation with topical and oral steroid therapy, or with ocular reconstruction surgery when required.

Refractive changes after excimer laser phototherapeutic keratectomy.

PURPOSE: To study the visual and refractive changes in patients with superficial corneal opacities after excimer laser phototherapeutic keratectomy (PTK). SETTING: Eye Clinic, Kobe Kaisei Hospital, Kobe, Japan. METHODS: One hundred twelve eyes of 80 patients with superficial corneal opacities had PTK with the Nidek EC-5000 excimer laser system. All patients had routine ophthalmic examinations including uncorrected and Landolt best corrected visual acuity (BCVA) measurements, subjective and objective refractions, keratometry, EyeSys (Premier Laser Systems, Inc.) corneal topography performed before and 1 week and 1, 3, 6, and 12 months after PTK, and pachymetry performed before and 12 months after PTK. The change in refractive status within 12 months of PTK and the relationship between factors such as ablation depth, transition zone (TZ) setting, and use of masking agents and the amount of hyperopic shift were also assessed. RESULTS: The BCVA increased by more than 2 lines in 65.1% of eyes and by 1 line in 24.1%. The BCVA did not change in 12 eyes (10.8%) because of cataract or underlying retinal disease. A mean hyperopic shift of 3.42 +/- 1.15 diopters (D) (range 1.00 to 5.25 D) was seen in all eyes at 12 months. The hyperopic shift peaked 1 month after PTK and tended to decline after that; it stabilized at 12 months. CONCLUSION: Although PTK is a safe and efficient method for the treatment of superficial corneal opacities, induced hyperopia after the procedure remains a major problem. A shallow ablation depth (less than 100 microm), presence of a TZ setting, and use of a masking agent decrease the hyperopic shift significantly.

Alteration of the ocular surface with recurrence of granular/avellino corneal dystrophy after phototherapeutic keratectomy: report of five cases and literature review.

PURPOSE: To study the changes in ocular surface findings with recurrence after phototherapeutic keratectomy (PTK) in patients with Avellino and granular dystrophy. DESIGN: Observational case series. PARTICIPANTS: Five eyes of five patients with recurrent granular/Avellino corneal dystrophy after PTK seen at Kobe Kaisei Hospital were studied. INTERVENTION: The patients underwent routine ophthalmic examinations, corneal sensitivity measurements, tear film breakup time (BUT), Schirmer test, tear film lipid layer interferometry, and conjunctival impression cytology. MAIN OUTCOME MEASURES: The alterations of clinical features, tear function, and conjunctival impression cytology parameters with a recurrence after PTK were investigated. RESULTS: The average pre-PTK corneal sensitivity and tear film breakup time were low in all five patients. Tear film lipid layer interferometry grade and conjunctival squamous metaplasia displayed higher grades before PTK. All of these parameters improved gradually after PTK and were maintained until a recurrence, which was associated with further worsening of the corneal sensitivity, tear function, and impression cytology parameters. CONCLUSIONS: Although PTK improves the ocular surface health in granular/Avellino corneal dystrophies, recurrence of the initial dystrophy is associated with decline of the ocular surface health parameters. Our findings also suggest that corneal epithelium is most probably involved in the recurrence of the disease process in Avellino/granular corneal dystrophy.

Tear function and ocular surface changes in noninsulin-dependent diabetes mellitus.

PURPOSE: To describe the ocular surface disorder in patients with diabetes. DESIGN: A prospective, case-controlled study. PARTICIPANTS: Eighty-eight eyes of 50 noninsulin-dependent diabetes mellitus patients seen at the Department of Ophthalmology, Kobe University School of Medicine, from September 1998 through February 1999, and 40 eyes of 20 healthy control individuals were studied. INTERVENTION: All subjects underwent routine ophthalmic examinations, corneal sensitivity measurements, Schirmer test, tear film break-up time (BUT) analysis, and conjunctival impression cytologic analysis. MAIN OUTCOME MEASURES: Patients and control subjects were compared for corneal sensitivity, tear function parameters, goblet cell density, and squamous metaplasia grade. The relation of diabetic peripheral neuropathy, metabolic control, duration of disease, and status of retinopathy to the ocular surface disorder was also noted. RESULTS: The mean corneal sensitivity was significantly lower in diabetic patients, diabetic patients with peripheral neuropathy, and poorly controlled diabetes compared with control subjects (P < 0.001). The BUT and Schirmer test values were also significantly lower in the diabetic group, in patients with peripheral neuropathy and poor metabolic control. Impression cytologic analysis showed goblet cell loss and conjunctival squamous metaplasia, both of which again related to peripheral neuropathy, poor diabetic control, and decreased corneal sensitivity. The examined parameters did not relate to duration of disease or status of diabetic retinopathy. CONCLUSIONS: The ocular surface disease in diabetes is characterized by a disorder of tear quantity and quality, squamous metaplasia, and goblet cell loss, all of which seem to evolve in close proximity to the status of metabolic control and peripheral neuropathy.

Visual and tear function improvement after superficial phototherapeutic keratectomy (PTK) for mid-stromal corneal scarring.

PURPOSE: To study the changes in visual and tear film function following superficial excimer laser phototherapeutic keratectomy in patients with mid-stromal corneal scars. METHODS: Fourteen eyes of 14 patients with mid-stromal corneal scars seen at the Department of Ophthalmology at Kobe Kaisei Hospital underwent superficial phototherapeutic keratectomy (PTK). The subjects underwent routine ophthalmic examinations, corneal sensitivity measurements, tear film break-up time (BUT), Schrimer test and tear film lipid layer interferometry. Thirty eyes of 15 normal control subjects were also studied. The patients and the control subjects were compared for pre-PTK tear function parameters and tear film lipid layer interferometry grade. The alterations in these parameters within 6 months following PTK were also determined. RESULTS: Visual improvement was achieved in 12 eyes (86%). A hyperopic shift was observed in all eyes. The average pre-PTK corneal sensitivity and tear film BUT were lower in patients compared with control subjects before PTK. Tear film lipid layer interferometry grades were also higher in the patients than the controls before PTK. All these parameters improved gradually and significantly after PTK. Schirmer test results did not show any significant alterations after PTK. CONCLUSION: We conclude that PTK is an effective means of treating corneal scars and attaining visual improvement, even in cases with deeper corneal involvement, and may obviate the need for corneal transplantation. Simultaneous improvements in corneal sensitivity and tear film stability suggest favourable effects of PTK on the ocular surface.

Ocular surface changes after excimer laser phototherapeutic keratectomy.

PURPOSE: To study the ocular surface disorder in patients with Avellino, granular, and lattice dystrophy, band keratopathy, and corneal leukoma before and after excimer laser phototherapeutic keratectomy. DESIGN: A prospective case-controlled study. PARTICIPANTS: A total of 45 eyes of 33 patients with superficial corneal opacities seen at Kobe Kaisei Hospital, Department of Ophthalmology, and 40 eyes of 20 normal control subjects were studied. INTERVENTION: The subjects underwent routine ophthalmic examinations, corneal sensitivity measurements, tear film break up time (BUT), Schirmer test, tear film lipid layer interferometry, and conjunctival impression cytology. MAIN OUTCOME MEASURES: The patients and the control subjects were compared for prephototherapeutic keratectomy (PTK) tear function parameters, tear film lipid layer interferometry grade, goblet cell density, and conjunctival squamous metaplasia grade. Alterations of these parameters within 3 months after PTK were also looked for. RESULTS: The average pre-PTK corneal sensitivity and tear film break up time were lower in patients compared with control subjects before PTK. Tear film lipid layer interferometry grade and conjunctival squamous metaplasia grades were higher in the patients than the controls before PTK. All these parameters improved gradually and significantly after PTK. Goblet cell density was significantly lower in the patients compared with controls before PTK. Schirmer test results and goblet cell density did not show any significant alterations after PTK. CONCLUSIONS: Concurrent improvements in corneal sensitivity, tear film break up time, lipid layer interference grades, and conjunctival squamous metaplasia grades all point to the favorable effects of PTK on the ocular surface by improving the stability of the tear film and ocular surface health through attainment of a regular corneal surface and probably inducing qualitatively/quantitatively better mucin production by a healthier epithelium after PTK.

[The effect of substance P with insulin-like growth factor-1 on corneal epithelial cell proliferation].

PURPOSE: To elucidate the pathogenesis of neuroparalytic keratopathy, we examined the effect of substance P (SP) on corneal epithelial cell proliferation in comparison with that of insulin-like growth factor-1 (IGF-1) in vivo and in vitro. METHODS: In the in vivo study, the epithelium of rabbit cornea was removed mechanically and treated with eye drops containing SP, IGF-1, SP + IGF-1, or physiological saline as a control. Corneas were excised 48 hours after the removal of the epithelium, labeled with 3H-thymidine, and subjected to autoradiography. An in vitro study was also performed by culturing rabbit corneal epithelial cells in culture medium containing SP with or without IGF-1 and labeling cells with 3H-thymidine for a subsequent autoradiographical study. FINDINGS: In the in vivo study, SP in combination with IGF-1 enhanced the healing of rabbit corneal epithelial defect. 3H-thymidine autoradiography revealed that in both in vivo and in vitro studies, SP + IGF-1 stimulated corneal epithelial cell proliferation, but SP or IGF-1 alone did not. CONCLUSION: These results indicate that SP enhances the stimulatory effect of IGF-1 on corneal epithelial cell proliferation and accelerates corneal epithelial healing.

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.

[Proliferation of corneal epithelial cells in diabetic rats].

In order to elucidate the mechanisms of diabetic corneal epitheliopathy, we investigated the proliferation of corneal epithelial cells of streptozotocin-induced diabetic rats in the 1st, 2nd, 3rd and 6th months after the onset of diabetes using 3H-thymidine autoradiography. After the 1st month in diabetic rats, histological examination revealed that corneal epithelial layer was thin, and proliferation of corneal epithelial cells was decreased compared with that of normal untreated rats. After the 2nd month, proliferation of corneal epithelial cells showed no difference from normal rats. After the 3rd month in diabetic rats, the attachment of the epithelial layer to the stroma was loose and proliferation of corneal epithelial cells was increased compared with that of normal untreated rats. After the 6th month, proliferation of corneal epithelial cells showed no difference between diabetic rats and normal rats. We suggest that increased turnover rate of corneal epithelial cells may account for increased proliferation of corneal epithelial cells in diabetic rats during the 3rd month.

Impression cytology in atopic dermatitis.

PURPOSE: This study aimed to describe the ocular surface disorder in patients with atopic dermatitis (AD). DESIGN: A prospective case-controlled study. PARTICIPANTS: A total of 44 patients with active AD seen at Kobe University School of Medicine, Department of Ophthalmology, during 1994 through 1996 and 22 normal control subjects were studied. INTERVENTION: The subjects underwent routine ophthalmic examinations, tear film break-up time (BUT), Schirmer test, and conjunctival impression cytology. MAIN OUTCOME MEASURES: Patients and control subjects were compared for tear function parameters, goblet cell density, and conjunctival squamous metaplasia grade. The relation of duration and recurrences of AD to the ocular surface disorder also was looked for. RESULTS: The duration of atopic disease ranged from 18 to 32 years (mean, 22.8 years). The average for exacerbations was 4.5 times. Chronic allergic conjunctivitis with superficial punctate keratitis was the most frequent clinical presentation. The BUT and Schirmer test values were significantly lower in patients with AD compared with those of the control subjects. Impression cytology showed goblet cell loss and conjunctival squamous metaplasia, both of which related to the number of recurrences of AD rather than the duration of disease. Facial atopy and allergic keratoconjunctivitis (AKC) related to the metaplasia of the ocular surface (P < 0.001). Patients with reduced goblet cell density also showed low BUT levels (P < 0.001). CONCLUSION: Ocular surface disorder of AD characterized by goblet cell loss and conjunctival squamous metaplasia seemed to evolve independently of the duration of disease but worsen with increased number of flare-ups. Direct epithelial damage by the allergic reaction, disorder of tear quality, and quantity may be important in the genesis of the atopic ocular surface disease.

[Capsaicin-induced corneal epithelial changes in rats].

To elucidate the mechanisms by which corneal sensory denervation causes corneal epithelial disorders, we investigated corneal epithelial changes in rats injected with capsaicin, which is known to desensitize the primary sensory neurons. Neonatal rats were injected with capsaicin (100 mg/kg) or only the vehicle as a control on the 2nd day after birth. Corneas were excised after 7-28 days and subjected to gold chloride staining. 3H-thymidine autoradiography, or immunohistochemistry using anti-substance P (SP) antibody. The results indicated poor attachment of corneal epithelium, decreased corneal nerve ending density, decreased 3H-thymidine uptake by epithelial cells, and decreased expression of SP in the epithelial layer in rats injected with capsaicin compared with the control rats. This suggests that decreased proliferation of corneal epithelial cells associated with decreased SP as well as poor attachment of the epithelium is one of the causes of neuroparalytic keratopathy.

[Expression of Mn-SOD mRNA in streptozotocin-induced diabetic rat cornea by in situ hybridization].

The pathogenesis of diabetic corneal epitheliopathy, one of the ocular complications frequently seen in diabetes patients, still remains to be elucidated. Hyperglycemia causes glycation of various proteins leading to the formation of superoxide radicals (O2.-). Copper, zinc-superoxide dismutase (Cu, Zn-SOD), a scavenger of superoxide radicals, whose function is complementary to manganese-SOD (Mn-SOD), is inactivated during glycation. As a first step to clarify whether depressed antioxidant activity is associated with diabetic corneal epitheliopathy or not, we investigated the expression of Mn-SOD mRNA (messenger ribonuclic acid) in streptozotocin-induced diabetic rat cornea by in situ hybridization using a digoxigenin-labeled Mn-SOD cDNA probe. Mn-SOD mRNA was detected in epithelial cell layer and endothelial cell layer of both diabetic rat cornea and normal rat cornea. However, the expression of Mn-SOD mMRA in the epithelial cell layer of diabetic rat cornea was weaker than that of normal rat cornea. These results suggest that decreased Mn-SOD activity might be one of factors causing diabetic corneal epitheliopathy.

[The effect of hyaluronic acid on keratocyte proliferation].

Our previous study demonstrated that during healing of penetrating corneal incision, hyaluronic acid (HA) appears at the wound area with massive infiltration of activated keratocytes, suggesting a possible role of HA in keratocyte proliferation. In the present study, we investigated the effect of HA on keratocyte proliferation. A penetrating incision was made in the center of rabbit corneas. Wounded corneas were treated with HA eye drops or physiological saline every 2 hours for 24 hours. Then the corneas were excised, labeled with 3H-thymidine for 4 hours, and subjected to autoradiography. Rabbit keratocytes were cultured in chamber slides in TC199 medium alone or in TC199 containing HA for 24 hours, labeled with 3H-thymidine for 4 hours, and subjected to autoradiography. In the corneas treated with HA, the number of keratocytes incorporating 3H-thymidine was significantly higher than in the control corneas. The rate of 3H-thymidine uptake in keratocytes cultured with any concentration of HA was higher than that of the control. Both in vivo and in vitro studies demonstrated stimulatory effect of HA on keratocyte proliferation. It is possible that HA might promote corneal stromal wound healing by stimulating keratocyte proliferation.

Corneal endothelial cell proliferation and migration after penetrating keratoplasty in rabbits.

The proliferation of the host endothelial cells during healing after penetrating keratoplasty (PKP) was investigated by exchange PKP in two groups of adult rabbits. After the endothelia of group A rabbits were selectively damaged by intracameral injection of benzalkonium chloride (BAK), grafts were made and transplanted to group B, untreated normal rabbits (damaged graft group). Grafts from group B rabbit eyes had already been made and these subsequently were transplanted to group A rabbits (normal graft group). Corneas were excised 4, 7, 14 and 28 days postoperatively, labeled with 3H-thymidine and subjected to autoradiography. The results indicated that in corneas with grafts damaged with BAK (damaged graft group), normal host endothelial cells proliferated and migrated into the damaged graft 4 days after surgery. In the normal graft group, the endothelial cells of the graft did not migrate to the damaged host cornea. On day 28, a monolayered apparently normal endothelium was regenerated in the damaged graft group. These results suggest that the proliferation of host corneal endothelial cells is vital in the endothelial healing of the graft after PKP in rabbits.

[The effect of epidermal growth factor on keratocytes during healing of corneal penetrating incision].

We investigated the effect of epidermal growth factor (EGF) on keratocytes during corneal wound healing focusing on cell proliferation. A penetrating linear incision was made in the center of rabbit corneas. The corneas were then treated with eye drops of recombinant human EGF (10 micrograms/ml) or physiological saline (control) four times a day. After 1, 2, 3, and 7 days, the corneas were excised, labeled with 3H-thymidine (10 microCi/ml) at 37 degrees C for 4 hours and subjected to autoradiography. The results demonstrated increased number of keratocytes incorporating 3H-thymidine on the 1st, 2nd, 3rd and 7th days of healing and accelerated stromal wound healing in corneas treated with EGF compared with the controls. Thus, EGF stimulates of proliferation keratocyte and promotes corneal stromal wound healing.

[Localization of Mn-SOD mRNA in rat cornea by in situ hybridization].

We investigated the localization of Mn-SOD mRNA in the rat cornea under physiological conditions using in situ hybridization. A Mn-SOD cDNA probe was synthesized by polymerase chain reaction. Slot blot analysis was performed to confirm that the cDNA probe hybridizes with rat Mn-SOD mRNA. Frozen sections of rat cornea were subjected to in situ hybridization using 3H-labeled Mn-SOD cDNA probe. The results demonstrated the expression of Mn-SOD mRNA in the rat corneal epithelial layer. We suggest that corneal epithelial cells are constantly exposed to active oxygen stress even under physiological conditions and synthesize Mn-SOD to protect themselves from the stress.

[Corneoscleral wound healing after self-sealing cataract surgery--2. Cellular proliferation].

We investigated histologically wound healing after self-sealing cataract surgery, focusing on cell proliferation. A scleral pocket and internal corneal flap were made according to Ernest's method in rabbit eyes on one side. After phacoemulcification procedure was performed, balanced salt solution (BSS plus) was injected to self-seal the wound (self-sealing group). After the same procedures were performed in the contralateral eyes, a horizontal 9.0 Nylon suture was placed in the wound (suture group). On various days after operation, the eyes were analyzed by corneal topography and enucleated. The corneo-scleral tissues were labelled with 3H-thymidine (10 microCi/ml) at 37 degrees C for 4 hr in Dulbecco's minimum essential medium, fixed with 4% paraformaldehyde and subjected to autoradiography. On the first day after operation, the scleral stromal fibroblasts at the scleral side and keratocytes at the corneal side incorporated 3H-thymidine. The 3H-thymidine uptake ratio was the highest on the first day and then gradually decreased. On the seventh day after operation, this incidence was higher in the suture group than in the self-sealing group, possibly due to the influence of the suture. We suggest that the difference in cellular proliferation during wound healing between the two groups might affect late postoperative astigmatism.