[Treatment of uveitis-associated refractory ocular hypotony with topical ibopamine]

BACKGROUND: Ibopamine is a non-selective dopamine- and adrenalin-receptor agonist that has been shown to cause pupillary dilation and an increase in aqueous humour secretion. This novel drug can be used as a mydriatic agent, as a provocative test in open-angle glaucoma, and for the treatment of persisting ocular hypotony. HISTORY AND SIGNS: This 47-year-old man had a history of uveitis associated with Crohn's disease. Six years after deep sclerectomy for uveitic secondary glaucoma, he developed severe hypotony in his left eye with drop of visual acuity (VA). The hypotony did not respond to topical steroid treatment. 2 % Ibopamine solution was ordered t. i. d. concomitant to 1 % prednisolone acetate. THERAPY AND OUTCOME: Intraocular pressure (IOP) began to rise after 3 weeks of Ibopamine treatment and returned to normal (12 mmHg) with continuous recovery of VA after 8 weeks. Ibopamine was discontinued at an IOP of 16 mmHg after a course of 12 weeks. IOP and VA remained stable during the 12-month follow-up period. CONCLUSIONS: Ibopamine 2 % eye drops in combination with topical steroids are a therapeutic option in uveitis-associated ocular hypotony.

Ocular pulse amplitude in healthy subjects as measured by dynamic contour tonometry

OBJECTIVES: To test whether dynamic contour tonometry yields ocular pulse amplitude (OPA) measurements that are independent of corneal thickness and curvature, and to assess variables of observer agreement. METHODS: In a multivariate cluster analysis on 223 eyes, the relationship between central corneal thickness, corneal curvature, axial length, anterior chamber depth, intraocular pressure, sex, age, and OPA measurements was assessed. Intraobserver and interobserver variabilities were calculated from repeated measurements obtained from 8 volunteers by 4 observers. RESULTS: The OPA readings were not affected by central corneal thickness (P = .08), corneal curvature (P = .47), anterior chamber depth (P = .80), age (P = .60), or sex (P = .73). There was a positive correlation between OPA and intraocular pressure (0.12 mm Hg/1 mm Hg of intraocular pressure; P<.001) and a negative correlation between OPA and axial length (0.27 mm Hg/1 mm of length; P<.001). Intraobserver and interobserver variabilities were 0.08 and 0.02 mm Hg, respectively, and the intraclass correlation coefficient was 0.89. CONCLUSIONS: The OPA readings obtained with dynamic contour tonometry in healthy subjects are not influenced by the structure of the anterior segment of the eye but are affected by intraocular pressure and axial length. We found a high amount of agreement within and between observers.

Microcystic serous cystadenoma of the pancreas: a report of two cases with one of diffuse presentation

Microcystic adenoma or serous cystadenoma is an uncommon tumor and accounts for 1-2% of the exocrine neoplasms of the pancreas. Usually unifocal, they present as single, large, well-demarcated multiloculated cystic tumors, ranging in size from 1 to 25 cm. Multifocal variants or diffuse serous cystadenomas are extremely rare. We present 2 cases of which 1 is a diffuse variant affecting the body, tail and part of the neck of the pancreas. In both the patients the tumors were detected incidentally. We highlight on the diffuse variant in view of its rarity and present a review of literature. In this case the entire body and tail of the pancreas was spongy replaced by multicystic lobules and hyalinized fibrocollagenous stroma. The cysts were lined by low cuboidal glycogen containing bland cells. Such a unique presentation wherein the entire body and tail of the pancreas is replaced with multiple cysts is a diffuse presentation of microcystic adenoma and a search through literature revealed only 7 such cases among the 15 cases with multifocal presentation reported.

Characterization of retinal damage in the episcleral vein cauterization rat glaucoma model

Episcleral vein cauterization (EVC) is used in rats to generate a glaucoma model with high intraocular pressure (IOP). The long-term retinal damage in this glaucoma model, however, has not been accurately quantified. We report the location and amount of retinal ganglion cell (RGC) damage caused by (EVC) induced IOP elevation in two rat strains. IOP was raised in one eye of Wistar (N = 5) and Brown-Norway(B-N)(N = 7) rats by EVC and monitored monthly until IOP in contralateral eyes equalized at 5 months post-surgery. Animals were maintained for 3.5-4.5 additional months. B-N rats (N = 7) that had no EVC served as controls for this strain. Scotopic flash ERGs were recorded at baseline and just prior to euthanasia. Automated counts of all retrogradely labeled RGCs in retinal flat-mounts were determined and compared between contralateral eyes. RGC density maps were constructed and RGC size distribution was determined. Oscillatory potentials in the group of eyes which had elevated IOP were decreased at the time of euthanasia, when IOP had returned to normal. The group of normal B-N rats had similar RGC counts between contralateral eyes. In the experimental group the mean number of RGCs was not significantly different between control and experimental eyes, but 1 of 5 Wistar and 2 of 7 B-N experimental eyes had at least 30% fewer RGCs than contralateral control eyes. Total retinal area in B-N experimental eyes was higher compared to contralateral eyes. Cumulative IOP exposure of the experimental eyes was modestly correlated with RGC loss while oscillatory potentials appeared to be inversely related to RGC loss. In retinas with extensive (> 30% RGC loss) but not complete damage, smaller cells were preserved better than larger ones. The above results indicate that RGC loss in both Wistar and B-N strains is variable after a prolonged elevation of IOP via EVC. Such variability despite equivalent IOP levels and ERG abnormalities, suggests unknown factors that can protect IOP-stressed RGCs. Identification and enhancement of such factors could prove useful for glaucoma therapy.

Uveitic glaucoma and Rosai-Dorfman disease (sinus histiocytosis)

PURPOSE: To report a novel association of uveitic glaucoma with Rosai-Dorfman disease. METHODS: Case report. RESULTS: A 67-year-old Caucasian woman presented with a chronic bilateral granulomatous uveitis which did not respond to conventional topical steroid therapy. She also had raised intraocular pressures, glaucomatous optic disc changes and diffuse nodular fibrous skin lesions. Subsequent skin biopsy immuno-cytochemistry showed S-100 staining, consistent with Rosai-Dorfman disease. The uveitis and glaucoma were highly resistant to standard medical treatments, but completely resolved together with the systemic features of the disease after six months. CONCLUSIONS: Rosai-Dorfman disease has not previously been reported to cause uveitic glaucoma and should be considered in non-responsive cases presenting with a rash. The disease is entirely self-limiting and early diagnosis may therefore avoid unnecessary trabeculectomy and/or systemic immune suppression.

DYT1 mutations amongst adult primary dystonia patients in Singapore with review of literature comparing East and West

BACKGROUND: Dystonia is a heterogenous group of movement disorders whose clinical spectrum is very wide. At least 13 different genes and gene loci have been reported. While a 3-bp deletion in the DYT1 gene is the most frequent cause of early limb-onset, generalized dystonia, it has also been found in non-generalized forms of sporadic dystonia. An 18-bp deletion in the DYT1 gene has also been reported. OBJECTIVES: We screened for the 3-bp and 18-bp deletions in the DYT1 gene among our sporadic, adult-onset primary dystonia patients in Singapore. We reviewed the literature to compare the frequency of DYT1 mutation between the East and the West. METHODS: We screened 54 patients with primary dystonia (focal: n=41; segmental: n=11; multifocal: n=1; generalized: n=1) for the deletions in the DYT1 gene. A careful review of all published literature on DYT1 screening among sporadic, non-familial, non-Ashkenazi Jewish patients was done. RESULTS: We did not detect any mutations in the exon 5 of the DYT1 gene in any of our patients. The frequency of DYT1 mutation amongst Asians (1.0%) was comparable to the West (1.56%) (p=NS). CONCLUSIONS: DYT1 mutations are uncommon amongst adult primary dystonia patients in Singapore.

Necrotising encephalitis in a French bulldog

A 20-month-old, female French bulldog was presented with a three-month history of generalised seizures and progressive ataxia with occasional falling over on either side. Neurological examination revealed signs, suggesting a multifocal intracranial lesion. Magnetic resonance imaging of the brain revealed two connected lesions on the left side of the caudal brainstem and a further lesion in the cerebrum. The dog was euthanased, and histopathological examination revealed lesions which closely resembled those of necrotising encephalitis in Yorkshire terriers. This is the first case describing this type of necrotising encephalitis in a French bulldog.

A case of necrotizing fasciitis with septic shock in a cat caused by Acinetobacter baumannii

A 4-year-old, neutered female, domestic shorthair cat admitted to the animal hospital for recurrent constipation presumed to be due to post-traumatic injuries, went into shock with signs including fever and ataxia followed by stupor. On the fifth day of hospitalization, the cat developed severe, diffuse oedema of the ventral abdomen with multifocal to coalescing erythematous areas and small vesicle formation. The results of bacteriological cultures of liver, spleen and kidney specimens led to the diagnosis of Acinetobacter baumannii sepsis. Histopathological findings of skin samples taken during necropsy showed an extensive epidermal and dermal necrosis with septic vasculitis and numerous intralesional gram-negative bacteria. Detection of the bla(OXA-51-like) gene specific for A. baumannii by PCR, performed retrospectively on samples of the deep layers of the skin, confirmed the presence of A. baumannii also in the cutaneous lesions. To our knowledge this is the first report of a necrotizing fasciitis with septic shock in a cat caused by A. baumannii.

Hepatoblastoma with a low serum alpha-fetoprotein level at diagnosis: The SIOPEL group experience

AIM OF THE STUDY: To investigate the characteristics of patients with hepatoblastoma and low serum alpha-fetoprotein (AFP) at diagnosis. PATIENTS AND METHODS: Inclusion of all 21 patients accrued onto SIOPEL trials, whose serum AFP was <100ng/ml at diagnosis. Slides of all 15 patients with available histological material were centrally reviewed. RESULTS: Median age: 10 months. Disease extension at diagnosis: PRETEXT group: II (3 patients), III (10 patients) and IV (8 patients). Extra-hepatic extension: 8 patients. Multifocal tumour: 8 patients. Histology at review: wholly epithelial subtype: 11/15 patients including nine with a small-cell undifferentiated histology. Outcome: only 9 patients achieved a partial response and 16 died. Median survival: 4.4 months. Two-year overall survival: 24% (confidence interval 10-45%). CONCLUSION: This study clearly identifies patients with hepatoblastoma and low serum AFP at diagnosis as a high-risk subgroup with extensive disease at diagnosis, poor response to chemotherapy and a poor outcome.

Therapy resistant neonatal seizures, linear vesicular rash, and unusually early neuroradiological changes: incontinentia pigmenti : A case report, literature review and insight into pathogenesis

CASE PRESENTATION: A substance abusing G2P1 mother spontaneously delivered at term an appropriate for gestational age girl. Neonatal seizures appeared at 21 hours and empiric anticonvulsive and antimicrobial treatment was started. At 25 hours, first vesicles appeared. While routine evaluations remained normal, a head CT revealed multifocal ischemic injuries, and a later MRI showed multifocal petechiae and diffusion abnormalities in the corticospinal tracts. The clinical diagnosis of incontinentia pigmenti (stage 1) was secured by histopathology. Follow-up at 13 months showed global developmental delay. DISCUSSION: We discuss the unusually early bilateral, fronto-occipital corticomedullar ischemias (CT day 3). On the MR imaging (day 7) extensive symmetric cerebral corticomedullar destruction and diffusion sequences with corticospinal tracts abnormalities are seen, which then evolve (day 26) to extensive symmetric cerebral destruction. We review the literature, genetics, suspected pathophysiology and possible neonatal manifestation. CONCLUSION: Incontinentia pigmenti is rare and, therefore, diagnosis is frequently delayed. Nevertheless, in the setting of therapy refractory seizures, excluded infections, and linear vesicular rash, a high index of suspicion is needed. This is the first report of simultaneous corticomedullar involvement as early as the third day of life.

Long-term outcome of trans-scleral diode laser cyclophotocoagulation in refractory glaucoma

BACKGROUND: Long-term outcome and complications of diode laser cyclophotocoagulation (DCPC) may be important, since eyes, once treated with DCPC, are less likely to be subjected to other types of interventions in the further follow-up. METHODS: Retrospective review of 131 eyes of 127 patients treated from 2000 through 2004. Success was defined as intraocular pressure (IOP) at last visit 6-21 mm Hg; hypotony: IOP

Novel pressure-to-cornea index in glaucoma

BACKGROUND: Several conversion tables and formulas have been suggested to correct applanation intraocular pressure (IOP) for central corneal thickness (CCT). CCT is also thought to represent an independent glaucoma risk factor. In an attempt to integrate IOP and CCT into a unified risk factor and avoid uncertain correction for tonometric inaccuracy, a new pressure-to-cornea index (PCI) is proposed. METHODS: PCI (IOP/CCT(3)) was defined as the ratio between untreated IOP and CCT(3) in mm (ultrasound pachymetry). PCI distribution in 220 normal controls, 53 patients with normal-tension glaucoma (NTG), 76 with ocular hypertension (OHT), and 89 with primary open-angle glaucoma (POAG) was investigated. PCI's ability to discriminate between glaucoma (NTG+POAG) and non-glaucoma (controls+OHT) was compared with that of three published formulae for correcting IOP for CCT. Receiver operating characteristic (ROC) curves were built. RESULTS: Mean PCI values were: Controls 92.0 (SD 24.8), NTG 129.1 (SD 25.8), OHT 134.0 (SD 26.5), POAG 173.6 (SD 40.9). To minimise IOP bias, eyes within the same 2 mm Hg range between 16 and 29 mm Hg (16-17, 18-19, etc) were separately compared: control and NTG eyes as well as OHT and POAG eyes differed significantly. PCI demonstrated a larger area under the ROC curve (AUC) and significantly higher sensitivity at fixed 80% and 90% specificities compared with each of the correction formulas; optimum PCI cut-off value 133.8. CONCLUSIONS: A PCI range of 120-140 is proposed as the upper limit of "normality", 120 being the cut-off value for eyes with untreated pressures or=22 mm Hg. PCI may reflect individual susceptibility to a given IOP level, and thus represent a glaucoma risk factor. Longitudinal studies are needed to prove its prognostic value.

Mechanisms of unexpected death and autopsy findings in Leigh syndrome (subacute necrotising encephalomyelopathy)

A 21-year-old previously-well woman who was undergoing medical investigations for problems with balance and suspected multiple sclerosis, developed a headache and breathing difficulties, and died suddenly and unexpected at home. The autopsy was unremarkable except for pulmonary and cerebral oedema. However, subsequent microscopy of the brain revealed characteristic features of Leigh syndrome with multifocal areas of astrogliosis, capillary proliferation, and parenchymal vacuolation. While Leigh syndrome is more commonly diagnosed in infancy, manifestations may occur throughout early life into adulthood. Sudden and unexpected death is a rare presentation that may be associated with cerebral necrosis and oedema. An awareness of the variable manifestations of Leigh syndrome is necessary in forensic practice as not all cases will present in a typical manner and sudden death may occur before a diagnosis has been established. The heritable nature of this condition makes accuracy of diagnosis essential.

[Positive ibopamine provocative test in normal-tension glaucoma suspects]

BACKGROUND: Ibopamine is an alpha-adrenergic agent and causes an elevation of intraocular pressure in eyes with increased outflow resistance. It has been proposed as a test substance for the detection of early ocular hydrodynamic disorders. PATIENTS AND METHODS: A total of 64 normal-tension glaucoma suspect eyes without anti-hypertensive treatment were enrolled. A daily pressure curve was registered with measurements at 7:00 am, 8:00 am, 12:00 am, 17:00 pm using an applanation tonometer and a contour tonometer followed by instillation of ibopamine 2% in both eyes. Tonometry was performed every 15 minutes during the following hour. An IOP increase of > 2.0 mmHg was considered positive. RESULTS: The positive test group showed a significant pressure increase from 18.04 to 22.06 mmHg. Ocular pulse amplitude increased from 2.96 to 3.97 mmHg and was positively correlated with the pressure. Intraocular pressure was unchanged in the negative test group. Central corneal thickness was not significantly different in the two groups (p = 0.32). CONCLUSIONS: Ibopamine 2% eye drops have a positive pressure effect in 50% of suspected normal-tension glaucoma eyes and may differentiate between eyes with normal trabecular outflow capacity and eyes with increased resistance in the trabecular meshwork that are prone to pressure peaks and deterioration to glaucoma.

Increased plasma endothelin-1 levels in patients with progressive open angle glaucoma

AIM: To compare the plasma levels of endothelin-1 (ET-1) between patients with primary open angle glaucoma with visual field progression despite normal or normalised intraocular pressure and patients with stabile visual fields in a retrospective study. METHODS: The progressive group consisted of 16 primary open angle glaucoma patients and the group with stable visual field consisted of 15 patients. After a 30 minute rest in a supine position, venous blood was obtained for ET-1 dosing. Difference in the plasma level of ET-1 between two groups was compared by means of analysis of covariance (ANCOVA), including age, sex, and mean arterial blood pressure as covariates. RESULTS: ET-1 plasma levels were found to be significantly increased in patients with deteriorating (3.47 (SD 0.75) pg/ml) glaucoma when compared to those with stable (2.59 (SD 0.54) pg/ml) visual fields (p = 0.0007). CONCLUSIONS: Glaucoma patients with visual field progression in spite of normal or normalised intraocular pressure have been found to have increased plasma endothelin-1 levels. It remains to be determined if this is a secondary phenomenon or whether it may have a role in the progression of glaucomatous damage.