Using diffuse weighted image and apparent diffusion coefficient in MRI for diagnosis of posterior ischemic optic neuropathy in a young male: a case report and literature review.

BACKGROUND: Posterior ischemic optic neuropathy (PION) is a rare cause of visual loss, especially in young patients who are more prone to inflammatory demyelinating optic neuritis (ON) compared to other types of optic neuropathy. The diagnosis of PION is usually a diagnosis of exclusion; however, the emergence of modern neuroimaging technique with diffuse-weighted image (DWI) and apparent diffusion coefficient (ADC) sequences in Magnetic Resonance Imaging (MRI) provides more evidence for accurate diagnosis and management. CASE PRESENTATION: A 30-year-old man with a history of hypertension and chronic renal failure secondary to glomerulonephritis presented with sudden onset of blurred vision, dyschromatopsia, pain, and positive relative afferent pupillary defect (RAPD) in the left eye for 1 week. He was initially admitted for steroid pulse therapy and was further monitored due to suspicion of optic neuritis oculus sinister (OS). However, his brain MRI revealed a focal high hyperintensity signal at the left optic nerve on the T2 DWI series. The area was corresponded with the hypointensity area in the ADC series, which was a powerful clue for PION. We explained the poor visual prognosis of PION to the patient after finishing steroid pulse therapy and referred him to the Nephrology and Neurology department for hypertension control to prevent additional hypertension related complication. CONCLUSIONS: The diagnosis of PION is usually a diagnosis of exclusion; however, carefully interpreting the DWI and ADC sequence in MRI may give the clinician more evidence for the definite diagnosis and leads to proper management.

Factors related to amblyopia in congenital ptosis after frontalis sling surgery.

BACKGROUND: Amblyopia is a main concern in children undergoing frontalis sling surgery for repairing congenital ptosis. This study aimed to evaluate factors related to amblyopia in children undergoing frontalis sling surgery. METHODS: IRB-approved retrospective review of children under the age of 12 who received frontalis sling surgery. Preoperative demographic data, strabismus, margin reflex distance 1 (MRD1), lid fissure height, sling type, refraction errors, surgical outcome and amblyopia were evaluated. RESULTS: This study included 48 eyelid procedures performed in 38 patients. Median age was 4.0 years. Etiology was congenital ptosis in 42 eyes (87.5%) and blepharophimosis in 6 eyes (12.5%). Mersilene mesh was the sling material used in 36 eyes (75%), silicone in 6 eyes (12.5%), and polytetrafluoroethylene (PTFE) in 6 eyes (12.5%). Mean duration of follow-up was 27.8 ± 25.0 months (range, 3 to 128 months). Amblyopia was observed in 17 eyes (35.4%) at the final follow-up. Factors significantly associated with final amblyopia included blepharophimosis (p = 0.017), preoperative MRD1 ≤ - 1.0 mm (p = 0.038), preoperative lid fissure ≤4.5 mm (p = 0.035), preoperative anisometropia (spherical equivalent) (p = 0.011), and postoperative astigmatism (p = 0.026). CONCLUSIONS: Study results suggest that blepharophimosis, preoperative MRD1 ≤ - 1.0 mm, preoperative lid fissure ≤4.5 mm, preoperative anisometropia (spherical equivalent), and postoperative astigmatism are associated with amblyopia after frontalis sling surgery in patients with congenital ptosis.

Ocular sparganosis mimicking an orbital idiopathic inflammatory syndrome.

Sparganosis is an infection by the parasitic tapeworm larvae of Spirometra species. Ocular sparganosis is a rare disease that is easily misdiagnosed. We reported a rare case of ocular sparganosis mimicking orbital idiopathic inflammatory syndrome at initial presentation. A 34-year-old female presented with rapid progressive swelling of her left eyelid and mild proptosis for the duration of one month. The other ocular examinations were normal and the thyroid function was normal. Magnetic resonance imaging revealed a fusiform enlargement and mild heterogenous enhancement of the superior oblique muscle of the left orbit. First she received prednisolone therapy and the proptosis partially improved. Six months later, a white, flat and wrinkled string like worm wriggled out from the caruncular conjunctiva of the left eye. The pathology results confirmed that the worm was a Spirometra species larva. After removal of the larva and treatment with praziquantel, the proptosis was resolved without recurrence. Ocular sparganosis is a rare disease and only a few case reports have been reported. The drug therapy has not been effective and the surgical removal is the principal therapy. Despite its rarity, ocular sparganosis should be considered as a possible cause of orbital inflammation in patients.

Antibiotic Choices for Pediatric Periorbital Cellulitis-A 20-Year Retrospective Study from Taiwan.

The delayed treatment of pediatric periorbital cellulitis may have severe consequences. In addition, the antibiotic efficacy against causative bacteria may change over time, and it is important to understand the appropriate antibiotic options for effective treatment in pediatric patients. We compared the changes in cultured bacteria and drug susceptibility tests between two decades, 2010-2019 and 2000-2009, to establish antibiotics for empirical use. The patient characteristics, etiologies, culture sites, and isolated bacteria, and the antibiotic susceptibility tests of the admitted pediatric patients (n = 207) diagnosed with preseptal and orbital cellulitis during 2000 to 2019, were recorded. Insect/animal bites (p = 0.084) showed an increasing trend, and sinusitis (p = 0.016) showed a significant decrease in the past decades. The most common bacteria were Staphylococcus aureus, and methicillin-resistant S. aureus (MRSA) infections increased in recent decades (p = 0.01). Moreover, we found that vancomycin was ideal for MRSA infections. The decreasing efficacy of oxacillin correlates with the increasing proportion of MRSA in pediatric periorbital cellulitis. Our study thus offers antibiotic choices against the most common isolates that can be administered before culture results are available.

Age influences the severity of Graves' ophthalmopathy.

This study compared the ocular manifestations of Graves' disease in different age groups and between genders. This was a retrospective study with a chart review of 210 patients seen in the Kaohsiung Veterans General Hospital Ophthalmology Department from 1990 to 2006. Clinical manifestations were recorded, scored, and compared between different age groups and between genders. A total of 77 male and 133 female patients were included. The mean age of the patients was 48.71 years (53.80 for male and 45.77 for female patients). The average ophthalmopathy score was 3.72 (4.51 for male and 3.26 for female patients). Age was positively correlated with ophthalmopathy score (p < 0.01). The male patients scored higher than the female patients, generally and in different age groups, but the difference did not reach a statistically significant level. One hundred and six patients underwent tests for thyroid-stimulating hormone receptor antibody (TRAb); 92 (86.80%) were positive, but the titers did not correlate with the severity of ophthalmopathy. In conclusion, the severity of Graves' ophthalmopathy is correlated with age (r = 0.286). Thus, older patients should be more closely followed up and more aggressively treated.

Nonarteritic ischemic optic neuropathy.

BACKGROUND: To describe the systemic and visual characteristics and prognosis in patients with nonarteritic ischemicoptic neuropathy (NAION) undergoing different treatments. METHODS: Retrospective chart review was performed in Kaohsiung Veterans General Hospital patients from 1995-2005 with a clinical diagnosis of NAION, including nonarteritic anterior ischemic optic neuropathy and posterior ischemic optic neuropathy (PION). There were 14 PION patients out of a total of 103 cases. The average age at disease attack was 61 years old, and the ratio of males to females was 1.24:1. Comorbid systemic diseases and visual function were recorded at both initial presentation and the later follow-up period. The final results were recorded and compared by the different treatments they received in 4 groups. RESULTS: In all, NAION usually affected people > 50 years old, without any difference between sexes. Presenting visual acuity, age, and different treatment modes had no direct influence on the final visual outcome. The most significant associated factor was hypertension. CONCLUSION: NAION is a serious illness; the visual deficit persists even with aggressive treatment.

Y-splitting with recession of lateral rectus versus lateral rectus recession in correcting upshoot in Duane retraction syndrome.

PURPOSE: To report the surgical effect in upshoot of Duane retraction syndrome (DRS) with corecession of horizontal rectus muscles with or without Y-splitting. PATIENTS AND METHODS: A retrospective chart review of six patients of DRS received muscle surgeries for upshoot in adducted position was performed. RESULTS: From 1994 to 2010, six Duane patients received muscle surgeries for upshoots of lesion eye in adduction. Their age of receiving surgery ranged from 5 to 41 years. Four of the patients were male, and five had their left eye involved. Three underwent recession of ipsilateral medial and lateral rectus (LR) muscles, and the other three also received Y-splitting of LR muscle when recession. One of the patients that received Y-splitting showed mild hypertropia at down gaze postoperatively, and another one had little improvement of exotropia at the primary position. All patients showed improvement of their upshoots and lid fissure narrowing in adduction as well as face turn. CONCLUSION: Postoperative improvements in abnormal head posture and upshoots were achieved with corecession of horizontal muscles with or without Y-splitting. Although Y-splitting of the LR muscle is an effective surgery, it might cause undesired complications.

Surgical results for consecutive exotropia.

PURPOSE: To evaluate the surgical results of medial rectus (MR) muscle advancement with or without recession of the antagonist muscle for consecutive exotropia. METHODS: Medical records of patients with consecutive exotropia (n = 27) were retrospectively reviewed. All patients received one-eye surgery with MR advancement, lateral rectus (LR) recession, or combined surgery. The pre- and post-operative angle of deviation was recorded. Characteristics were compared between groups. The follow-up period was at least 3 months. RESULTS: The overall successful rate was 62.96%, with 50% in MR advancement group, 60% in LR recession group, and 71.4% in combined group. Patients in combined group had larger preoperative deviation. There were comparable surgical results between patients with inferior oblique (IO) muscle overaction receiving correction simultaneously and patients without IO muscle overaction. CONCLUSIONS: The overall surgical successful rate for consecutive exotropia in this study was 62.96%. Combined MR advancement and LR recession yielded better results than MR advancement or LR recession alone although it was not statistically significant.

Incidence and prognostic factor of ethambutol-related optic neuropathy: 10-year experience in southern Taiwan.

To investigate the incidence and prognostic factors of ethambutol-related optic neuropathy (EON) in one medical center of southern Taiwan, a retrospective chart review study with 4803 newly diagnosed tuberculosis cases from January 2002 to July 2011 at one medical center hospital in southern Taiwan were reviewed. Of these patients, 1004 had ophthalmic records. Sixty-two cases (1.29%) experienced visual impairment and were diagnosed as EON with mean visual acuity of 0.86 ± 0.69 by logMAR. Sixteen of the 62 patients had a follow-up time > 6 months. Of these, eight patients (50%) showed visual improvement (an increase in visual acuity of ≥ 2 Snellen lines) after ethambutol was discontinued. Another eight patients (50%) showed no visual improvement. We analyzed multiple factors between the patients with and without visual improvement by logistic regression, including body weight, daily dose of ethambutol, duration of ethambutol use, cumulative dose of ethambutol, renal function, underlying disease of diabetes mellitus, hypertension, and initial visual acuity showed no statistically significant difference. In conclusion, the incidence of EON was 1.29%. Half of the patients showed visual improvement after discontinuation of ethambutol, and no obvious prognostic factors were found to facilitate the vision recovery. Ethambutol should be discontinued as soon as EON is suspected.

Ocular adnexal lymphoma: Five case reports and a literature review.

This article reports the clinical course and treatment of ocular adnexal lymphoma based on a retrospective review of five cases with a histologically approved ocular adnexal lymphoma at Kaohsiung Veterans General Hospital over 10 years. Extranodal B-cell lymphoma in the orbit, lacrimal gland, eyelid, or conjunctiva was found in these patients. Four of them were female, and they were aged 45-64 years. All patients were also consulted with hematologists for possible systemic involvement and therapeutic plan. The patient with retrobulbar and orbital apex involvement received systemic chemotherapy. The patient with lacrimal gland involvement experienced tumor recurrence after local excision, and therefore received adjuvant radiotherapy. The remaining three patients had localized lymphoma on the eyelid or bulbar conjunctiva, and they all showed no recurrence after surgical excision. The incidence of ocular adnexal lymphoma has risen worldwide over the last few decades. Although most cases are confined to ocular adnexal, some may also be associated with disseminated lymphoma. Accurate diagnosis and staging is mandatory for appropriate treatment. Generally speaking, localized and low-grade ocular adnexal lymphoma involved eyelid or conjunctiva seem to have good outcome after surgical excision only. Systemic chemotherapy should be considered in patients with advanced disease or systemic manifestations, and radiotherapy also offers a good choice for lacrimal gland lymphoma.

Effect of nordihydroguaiaretic acid on intracellular Ca(2+) concentrations in C6 glioma cells.

The effect of nordihydroguaiaretic acid (NDGA) on Ca(2+) signaling in C6 glioma cells has been investigated. NDGA (5-100 microM) increased [Ca(2+)]i concentration-dependently. The [Ca(2+)]i increase comprised an initial rise and an elevated phase over a time period of 4 min. Removal of extracellular Ca(2+) reduced NDGA-induced [Ca(2+)]i signals by 52+/-2%. After incubation of cells with NDGA in Ca(2+)-free medium for 4 min, addition of 3 mM CaCl2 induced a concentration-dependent increase in [Ca(2+)]i. NDGA (100 microM)-induced [Ca(2+)]i increases in Ca(2+)-containing medium was not changed by pretreatment with 10 microM nifedipine or verapamil. In Ca(2+)-free medium, pretreatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (1 microM) abolished 100 microM NDGA-induced [Ca(2+)]i increases. Inhibition of phospholipase C with 2 microM U73122 had little effect on 100 microM NDGA-induced Ca(2+) release. Several other lipoxygenase inhibitors had no effect on basal [Ca(2+)]i. Collectively, the results suggest that NDGA increased [Ca(2+)]i in glioma cells in a lipoxygenase-independent manner, by releasing Ca(2+) from the endoplasmic reticulum in a manner independent of phospholipase C activity and by causing Ca(2+) influx.

The anti-anginal drug fendiline elevates cytosolic Ca(2+) in rabbit corneal epithelial cells.

The effect of the anti-anginal drug fendiline on intracellular free Ca(2+) levels ([Ca(2+)](i)) in a rabbit corneal epithelial cell line (SIRC) was explored using fura-2 as a fluorescent Ca(2+) indicator. At a concentration above 1 microM, fendiline increased [Ca(2+)](i) in a concentration-dependent manner with an EC(50) value of 7 microM. The [Ca(2+)](i) response consisted of an immediate rise and an elevated phase. Extracellular Ca(2+) removal decreased half of the [Ca(2+)](i )signal. Fendiline induced quench of fura-2 fluorescence by Mn(2+) (50 microM), suggesting the presence of Ca(2+) influx across the plasma membrane. This Ca(2+) influx was abolished by La(3+) (50 microM), but was insensitive to dihydropyridines, verapamil and diltiazem. Fendiline (10 microM)-induced store Ca(2+) release was largely reduced by pretreatment with thapsigargin (1 microM) (an endoplasmic reticulum Ca(2+) pump inhibitor) to deplete the endoplasmic reticulum Ca(2+). Conversely, pretreatment with 10 microM fendiline abolished thapsigargin-induced Ca(2+) release. Fendiline (10 microM)-induced Ca(2+) release was not altered by inhibiting phospholipase C with 2 microM 1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122). Cumulatively, this study shows that fendiline induced concentration-dependent [Ca(2+)](i )increases in corneal epithelial cells by releasing the endoplasmic reticulum Ca(2+) in a phospholipase C-independent manner, and by causing Ca(2+) influx.

A suprasellar meningioma simulating atypical retrobulbar optic neuritis.

A 39-year-old female came with the chief complaint of acute decrease of left eye vision for the past 2 weeks. No history of systemic diseases or headache was complained. The visual acuity of the left eye was "hand motion", and rapidly responded to methylprednisolone therapy in 3 days. On tapering oral prednisolone, the visual acuity decreased again from 20/20 to light perception in the left eye. The magnetic resonance image (MRI) study showed a large suprasellar mass. The patient underwent craniotomy and removal of the tumor successfully, and the pathological report turned out to be a meningioma. The visual acuity of the left eye remained poor after the surgery. In conclusion, neuroimaging study is necessary in every case of presumed retrobulbar optic neuritis which shows atypical course. Early detection of a brain tumor may save the vision of the patient.

Optic neuritis: clinical analysis of 27 cases.

We retrospectively reviewed 27 cases diagnosed as idiopathic optic neuritis between 1992 and 2001 at Kaohsiung Veterans General Hospital to assess the clinical features, visual prognosis, neuroimaging, laboratory studies, and development of multiple sclerosis in Chinese patients with optic neuritis. Patient age ranged from 13 to 54 years (mean, 35.8 +/- 11.3 years). Five cases presented as bilateral optic neuritis and 22 as unilateral. Visual function improved gradually from 2 weeks after treatment. Twelve (44.4%) cases showed disc swelling and ocular pain was also noted in 44.4% of patients. All cases that underwent visual field and visual evoked potential tests showed abnormality in lesion eyes. Of the 23 cases that underwent neuroimaging studies, including computerized tomography (17 patients) and magnetic resonance imaging (6 patients), 10 revealed optic nerve thickening. Four cases (14.8%) developed multiple sclerosis during follow-up (mean, 4.3 years). The incidence of disc swelling was higher than that reported by the Optic Neuritis Treatment Trial, but the incidence of initial ocular pain, the presence of periventricular plaques, and the development of multiple sclerosis were lower in our study. The unilateral group had significantly better visual outcome than the bilateral group.

Elevated white blood cell count may predict risk of orbital implant exposure.

OBJECTIVE: To determine the risk factors for primary implant exposure after enucleation and evisceration in infected eyes. DESIGN: Retrospective, comparative case series. PARTICIPANTS: Patients who underwent enucleation or evisceration for infected eyes. METHODS: Records of patients who underwent enucleation or evisceration for infected eyes with placement of solid sphere implants were reviewed. Preoperative white blood cell (WBC) count, microbiologic laboratory results, clinical features, medical treatment, and surgical methods were recorded to evaluate the risk for implant exposure. RESULTS: Eighty-five infected eyes were collected. The mean age was 70.1 years. The positive culture rate was 69.4%. In 42 patients with endophthalmitis or panophthalmitis, the most common microorganisms were Pseudomonas aeruginosa in 6 cases (20.7%) and Klebsiella pneumoniae in 7 cases (24.1%). In 50 patients with keratitis or scleritis, the most common microorganisms were P. aeruginosa in 14 eyes (46.7%) and Fusarium in 4 eyes (13.3%). There was a 12.9% exposure rate for the 85 patients. Preoperative WBC count was significantly higher in patients with implant exposure compared with those without exposure (p = 0.04). Preoperative WBC count more than 9500 cells/L had significantly higher exposure (p = 0.001). CONCLUSIONS: Preoperative elevated WBC count was associated with higher risk for implant exposure. Primary implantation after enucleation or evisceration may be less safe in infected eyes with high preoperative WBC count.

Acquired paralytic strabismus in Southern Taiwan.

BACKGROUND: Third, fourth, and sixth cranial nerve (CN3, CN4, and CN6) palsies are not uncommon in neuro-ophthalmology. The time and quality of recovery depend on the causes of the cranial nerve palsy. The purpose of our study was to evaluate the causes and outcome of acquired paralytic strabismus (PS) in a southern Taiwan population. METHODS: This study involved a retrospective chart review of patients at Kaohsiung Veterans General Hospital from January 2006 through July 2009. A total of 196 patients were enrolled. Outcomes and recovery times were recorded for the patients who exhibited C3, C4, and C6 palsies. The patients were categorized into four etiologic groups: vascular, idiopathic, traumatic, and neoplastic. The onset of PS, its continuing medical management, recovery, and other outcomes were followed up in these patients over a period of up to 10 years. RESULTS: The mean age of the 196 patients enrolled was 58.35 ± 17.60 years (range 11-90 years), and the mean follow-up time was 13.6 months. Seventy-seven patients (39.29%) had CN3 palsy, 38 patients (19.39%) had CN4 palsy, and 81 patients (41.33%) had CN6 palsy. The most common causes were vascular diseases (35.20%), followed by trauma (33.67%), and idiopathic causes (21.94%). About 50% of the patients recovered within 6 months. Among the four etiologic groups of patients, the vascular group showed the best recovery: about half of the patients recovered within 3 months. Longer recovery periods were necessary for patients in the neoplastic group than for those in the traumatic, vascular, and idiopathic groups (p = 0.01; p < 0.001; p < 0.001, respectively). CONCLUSION: The prognosis for patients with PS depended mostly on the cause of their disease. Patients with PS attributable to a vascular cause had a better prognosis than the other patients, and those in the neoplastic group required the longest time to recover.

Surgical treatment of acquired esotropia in patients with high myopia.

Acquired esotropia with high myopia may be associated with superotemporal eyeball prolapse from the muscle cone and the subsequent shift of extraocular muscles limits the success of the traditional recession-resection surgery. In this study, we report two patients diagnosed with myopic strabismus fixus with esodeviation >90 prism diopter. Marked axial elongation of globes was present in both the patients. They received medial rectus muscle recession and hemi-Jensen procedure in both eyes. Postoperatively, they showed significant improvement in abduction, elevation, and ocular alignment. We found that the combination of medial rectus muscle recession and hemi-Jensen procedure was effective in treating patients with acquired large esotropia with high myopia.

Manifested strabismus in a case of Apert syndrome.

A full-term female baby was diagnosed as having Apert syndrome with craniosynostosis, hypertelorism, syndactyly, polydactyly, and cleft plate. At her first ophthalmic visit at 8 months old, she was noted to have bilateral exophthalmos with epiblepharon on her lower lids, exotropia, and right inferior oblique muscle overaction (IOOA) and manifested right dissociated vertical deviation (DVD). There was no keratopathy or optic neuropathy. Bilateral lateral rectus muscles and right inferior oblique muscle recession were performed with correction of bilateral epiblepharon at 1 year of age. Orthotropia was achieved postoperatively. However, recurrent exotropia with left inferior oblique muscle overaction and manifested left DVD developed 2 years later. We performed left medial rectus muscle resection and left inferior oblique muscle recession, and the patient maintained orthotropia. Her best-corrected visual acuity was 6/8.6 in the right eye and 6/7.5 in the left eye at the latest follow-up. Amblyopia, OD, was still noted. We report this case of Apert syndrome with exophthalmos, exotropia, and IOOA. The exophthalmos progressed as the patient grew, thus the strabismus pattern changed during follow-up. Frequent follow-up and titrated management may be needed for such case to ensure good binocular vision.

Extensive alveolar-type paranasal sinus and orbit rhabdomyosarcoma with intracranial invasion treated successfully.

We report a case of extensive paranasal sinus and orbit rhabdomyosarcoma (RMS) with intra-cranial invasion treated successfully with chemotherapy and radiotherapy. A 13-years-old male patient complained of painless and progressive proptosis of his left eye for two weeks. Ocular examination showed elevated intraocular pressure, limited extraocular movement, proptosis, and conjunctival ciliary injection in the left eye. Brain CT and MRI demonstrated a large enhancing soft tissue mass lesion with bone destruction involving left ethmoid sinus, nasal cavity, maxillary sinus, and orbital cavity with crossing of the midline to the right ethmoid sinus, nasal cavity, and intra-cranial invasion across the frontal base. The pathology of tumor biopsy revealed rhabdomyosarcoma, alveolar type. Systemic survey showed no evidence of distant metastasis. Then, the patient received combined radiochemotherapy with Taiwan Pediatric Oncology Group Rhabdomyosarcoma 2007 High-risk Treatment Protocol. No light perception in his left eye with optic disc atrophy was noted at the beginning of radiotherapy. After 44 weeks of combined radiochemotherapy, the tumor regressed, and no recurrence has been noted until now. In young patients with sudden-onset proptosis, RMS should be considered, and early diagnosis is crucial due to more effective prognosis with current radiochemotherapy protocol.

Ketoconazole-evoked [Ca2+]i rises and non-Ca2+-triggered cell death in rabbit corneal epithelial cells (SIRC).

The effect of ketoconazole on cytosolic free Ca2+ concentrations ([Ca2+]i) and proliferation has not been explored in corneal cells. This study examined whether ketoconazole alters Ca2+ levels and causes cell death in SIRC rabbit corneal epithelial cells. [Ca2+]i and cell viability were measured by using the fluorescent dyes fura-2 and WST-1, respectively. Ketoconazole at concentrations of 5 microM and above increased [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced partly by removing extracellular Ca2+. The ketoconazole-induced Ca2+ influx was insensitive to L-type Ca2+ channel blockers and protein kinase C modulators. In Ca2+-free medium, after pretreatment with 50 microM ketoconazole, thapsigargin-(1 microM)-induced [Ca2+]i rises were abolished; conversely, thapsigargin pretreatment nearly abolished ketoconazole-induced [Ca2+]i rises. Inhibition of phospholipase C with 2 microM U73122 did not change ketoconazole-induced [Ca2+]i rises. At concentrations between 5 and 100 microM, ketoconazole killed cells in a concentration-dependent manner. The cytotoxic effect of 50 microM ketoconazole was not reversed by prechelating cytosolic Ca2+ with BAPTA. In summary, in corneal cells, ketoconazole-induced [Ca2+]i rises by causing Ca2+ release from the endoplasmic reticulum and Ca2+ influx from unknown pathways. Furthermore, the cytotoxicity induced by ketoconazole was not caused via a preceding [Ca2+]i rise.