Should central serous chorioretinopathy be added to the list of ocular side effects of phosphodiesterase 5 inhibitors?

INTRODUCTION: Rare cases of central serous chorioretinopathy (CSC) associated with the intake of sildenafil citrate have been reported, although CSC is not included in the list of phosphodiesterase 5 (PDE5) inhibitor side effects. MATERIALS AND METHODS: We present a review of the literature and 2 cases of CSC in 2 men taking PDE5 inhibitors (vardenafil and tadalafil) for erectile dysfunction. In both cases chorioretinopathy appeared after intake of the inhibitor, resolved once the latter was discontinued, reappeared when the inhibitor was restarted and resolved once again after the inhibitor had been discontinued for the second time. DISCUSSION: PDE5 inhibitors used for male erectile dysfunction have been associated with ocular side effects including lid edema, hyposphagma, photophobia, mydriasis, dyschromatopsia, and nonarteritic anterior ischemic optic neuropathy. CSC was previously described in patients taking sildenafil citrate. Very recently, a case of CSC after tadalafil intake was reported. The relevant literature is reviewed and possible pathophysiologic mechanisms are discussed. CONCLUSION: The 2 presented cases of CSC after intake of vardenafil or tadalafil with positive dechallenge, rechallenge and second dechallenge reactions provide important arguments for considering CSC as a rare PDE5 inhibitor class-specific side effect.

Distinct mechanisms of form-from-motion perception in human extrastriate cortex.

The exquisite sensitivity of the human visual system to form-from-motion (FfM) cues is well documented. However, identifying the neural correlates of this sensitivity has proven difficult, particularly determining the respective contributions of different motion areas in extrastriate visual cortex. Here we measured visual FfM perception and more elementary visual motion (VM) perception in a group of 32 patients suffering from acute posterior brain damage, and performed MRI-based lesion analysis. Our results suggest that severe FfM perception deficits without an associated deficit of VM perception are due to damage to ventral occipito-temporal cortex (VOT), whereas associated deficits of FfM and VM perception are due to damage either in proximity to area MT+/V5 or an area including lateral occipital complex (LOC) and VOT. These data suggest the existence of at least three functionally and anatomically distinct regions in human visual cortex that process FfM signals.

Subretinal electrode implantation in the P23H rat for chronic stimulations.

BACKGROUND: In age related macular degeneration and inherited dystrophies, preservation of retinal ganglion cells has been demonstrated. This finding has led to the development of various models of subretinal or epiretinal implant in order to restore vision. This study addresses the development of a polyimide subretinal electrode platform in the dystrophic P23H rat in vivo. METHODS: A technique was developed for implanting a subretinal electrode into the subretinal space and stabilising the distal extremity of the cabling on the rat cranium in order to allow future electrical stimulations of the retina. RESULTS: In vivo imaging of the retina with the scanning laser ophthalmoscope demonstrated reabsorption of the surgically induced retinal detachment and the absence of major tissue reactions. These in vivo observations were confirmed by retinal histology. The extraocular fixation system on the rat cranium was effective in stabilising the distal connector for in vivo stimulation. CONCLUSION: This study demonstrates that a retinal implant can be introduced into the subretinal space of a dystrophic rat with a stable external connection for repeatable electrical measurements and stimulation. This in vivo model should therefore allow us to evaluate the safety and efficacy of electrical stimulations on dystrophic retina.

The murine flg gene encodes a receptor for fibroblast growth factor.

The human flg gene has been previously shown to encode a tyrosine kinase whose transcription in endothelial cells is regulated by the fibroblast growth factor (FGF). We report the cloning and sequencing of the murine flg which revealed that the full length transcript encodes a transmembrane receptor-like protein. The extracellular portion is composed of three homologous immunoglobulin-like domains, resembling the organization of the receptor for interleukin-1, and the cytoplasmic domain displays unique organization of tyrosine kinase sequences. An anti-peptide antibody directed to the carboxy-terminus of the flg protein recognized three fibroblast-cell proteins (p150, p130 and p105), that undergo phosphorylation in the immune-complex. Moreover, the antibody specifically immunoprecipitated two proteins (p145 and p120) that were covalently crosslinked to basic FGF, but only one (p155) of the two molecular forms of the receptor for acidic FGF. In situ hybridization analysis of mouse embryos (12.5 days p.c.) indicated that flg is transcribed in the prospective brain, areas of the face and the vertebral column. The latter exhibited progressive cranio-caudal concentration into the intervertebral discs. Taken together, these results strongly suggest that the flg gene encodes a receptor for fibroblast growth factor(s).

Differences between embryonic and adult Torpedo acetylcholine receptor gamma subunit.

Antibodies to a synthetic peptide corresponding to residues 346-359 of the Torpedo acetylcholine receptor (AChR) gamma subunit, were employed to compare the adult and embryonic receptor. This peptide contains a consensus phosphorylation site for cAMP-dependent protein kinase (PKA). The anti-peptide antibodies discriminated between adult and embryonic AChRs, and reacted preferentially with the adult gamma form. These observed immunological differences did not seem to stem from different phosphorylation states. Our results suggest that the embryonic Torpedo AChR may have a gamma-like subunit that differs from the known adult form of this subunit, at least in the specific region that contains the phosphorylation site for PKA.

Metastatic infiltration of nerves in the cavernous sinus.

Painful dysesthesia in association with ocular motor palsies characterized intraneural carcinomatous invasion in a 48-year-old man. Transcranial biopsy of the cavernous sinus stopped the pain; the specimen confirmed the diagnosis and provided the rationale for radiation therapy. One year after treatment, the patient was healthy and pain-free, with improved ocular motor function. The source of the carcinoma remains unknown.

Periodic downbeat nystagmus.

The authors observed a periodic downbeat nystagmus with a cycle of 3 minutes 30 seconds, beating downward for a period of 90 seconds every 2 minutes. It lasted 86 hours in a patient with severe hypomagnesemia associated with complications from scleroderma. There was no lesion on brain imaging, and an EEG performed during the nystagmus was normal, indicating that the most likely explanation for this periodic nystagmus is metabolic. This form of nystagmus may have resulted from severe hypomagnesemia, possibly associated with thiamine deficiency.

Statokinetic dissociation in lesions of the anterior visual pathways. A reappraisal of the Riddoch phenomenon.

With standard Goldmann perimetry, physiologic dissociation of kinetic and statis stimuli was first investigated in 15 normal subjects. Variable degrees of statokinetic dissociation (SKD) occurred for white and for red (achromatic perception) targets, but not for chromatic recognition of red. To analyze relative sensitivity of these stimuli in defining field defects, a set of "isopter equivalents," eg, white I2e, red II4c (achromatic perception), and red V4e (chromatic recognition) was empirically established in normal and in pathologic fields of 11 patients with compression of the anterior visual pathways. The "Riddoch phenomenon" (SKD) was documented in defective fields in all patients with tumors; SKD occurred for white or for red achromatic perception. The most sensitive technique for elaborating field defects proved to be static presentation of white or red stimuli (achromatic perception) and chromatic recognition of static or kinetic red. As a rapid, sensitive screening method, especially for subtle defects, we suggest the addition of chromatic recognition of kinetic red stimuli to the application of standard kinetic white stimuli. Our findings are discussed in light of current concepts of retinal ganglion cell physiology.

Threshold perimetry in tilted disc syndrome.

Twelve consecutive patients (17 eyes) with tilted disc syndrome underwent quantified visual field examination with the G1 Octopus program (Interzeag AG, Schlieren, Switzerland). Visual fields were abnormal in all cases. Although field loss was more pronounced in the superotemporal quadrant (P less than .001), it also involved the other three quadrants, thus demonstrating that optic nerve hypoplasia in tilted disc syndrome is apparently not entirely sectorial. Linear regression analysis showed that an increase in mean defect correlated with increase in myopic refractive error (P less than .05). However, the increase in myopic refractive error was found to be related to a decrease in corrected loss variance (P less than .05), indicating that in tilted discs with higher myopia, field loss is more homogeneous. With this series of patients, short-term fluctuation was within normal ranges in all visual fields, showing that this may be an additional clue for differential diagnosis from acquired disorders.

Corneal hypoesthesia.

Decreased corneal sensitivity is an important clinical parameter in neuro-ophthalmological evaluation. It may be associated with such disorders as diabetes, Herpes simplex keratitis, and myasthenia gravis, with corneal toxicity via chemical exposure or ocular drug therapy, and with ocular surgery. In this review, methods and precautions involved in measuring corneal sensitivity are summarized, and the clinical conditions in which corneal hypoesthesia may exist are discussed.

The vanishing of the sun: a manifestation of cortical plasticity.

In Monet's painting impression. Rising Sun, when one steadily fixates the image of a sailor in the center of the picture for several seconds, the solar disk progressively disappears, being replaced in both brightness and color by the surrounding sky. This "filling-in" phenomenon reflects a process of cortical remapping, similar to the one that occurs in the presence of visual field defects. Filling-in is largely ignored by clinicians, despite its major implications in ophthalmologic practice, especially the nonrecognition of visual field deficits.

Ganglion cells from chick retina display multiple functional nAChR subtypes.

We have examined the properties of nicotinic acetylcholine receptors in embryonic chick retinal ganglion cells. Ganglion cells, identified according to morphological and physiological criteria, displayed spontaneous or induced action potentials. In 94/99 cells acetylcholine pulses evoked responses. In current clamp mode, acetylcholine provoked membrane depolarization and triggered action potentials. Under voltage clamp conditions, acetylcholine evoked inward currents that were readily blocked by d-tubocurarine. Antagonists specific for homomeric (alpha-bungarotoxin) and heteromeric (dihydro-beta-erythroidine) receptors revealed that ganglion cells express multiple functional receptor subtypes. These findings demonstrate that ACh modulates the electrical activity of these cells and is likely to mediate synaptic transmission. The presence of multiple receptor subtypes may contribute to processing and transmission of information in the retina.

Modified composition of major ontogenetically regulated mRNAs and proteins in the cerebellum of old and of staggerer mice.

The macromolecular composition of the cerebellum was examined in young and old mice, and in staggerer mutant mice, as compared with their background control strain. We examined the in vitro translation products of cerebellum mRNA, which reflect the biosynthetic potential of cell bodies endogenous to the cerebellum. Simultaneously, we examined the composition of the major cerebellum proteins, which includes the contribution of incoming fibers, in addition to the proteins composing cerebellar cells. Changes in the concentrations of various major proteins and a significant reduction in the translational efficiency of RNA were observed in the cerebellum of old BALB/c mice. This reduction probably does not reflect a specific damage to interneurons, since RNA from the cerebellum of 5-month-old staggerer mice was as efficient in translation in vitro as RNA from the cerebellum of mice from C57B6J normal background strain. Several of the major cerebellar proteins were identified by 2-dimensional gel electrophoresis. Changes were observed at the level of and the microheterogeneity of tubulin from the cerebellum of old, as compared with young mice. The aging-related modifications in cerebellar tubulin may be regulated at the level of mRNA, since mRNA from the cerebellum of old mice appeared to produce lower amounts of a polypeptide band co-migrating with tubulin. When compared with translation products directed by mRNA from normal cerebellum, most of the major identified polypeptides produced by mRNA from staggerer cerebellum showed marked differences in their relative intensity. Thus, this mutation appears to change the composition of cerebellar mRNA. These differences were analyzed together with previously obtained data on the composition of translation products during development of normal and of irradiation-agranulated cerebellum. The combined analysis of cerebellar mRNA products permits us to tentatively assign defined protein markers to specific cerebellar cell types and periods in development.

Variations in gene expression during development of the rat cerebellum.

Prominent variations in the concentration and composition of poly (A)-containing messenger RNA were found to occur during the postnatal development of the rat cerebellum. The concentration of mRNA (microgram/g cerebellar tissue) was determined to be the highest on the tenth postnatal day, at the onset of synaptogenesis. Short non-abundant mRNA chains continuously increase in amount during cerebellar development, while the fraction of long translatable mRNAs decreases. The overall ability of cerebellar mRNA to stimulate the incorporation of [35S]methionine into polypeptides in reticulocyte lysate apparently does not change. The proteins synthesized in vitro by cerebellar mRNA from different developmental stages were therefore analyzed by single and 2-dimensional gel electrophoresis. The diversity of these proteins and the levels of many of them were found to vary with cerebellar development. The newly synthesized brain forms of enolase and creatine kinase were identified by their migration coordinates in the 2-dimensional protein gels, and increase in the abundance of their directing mRNAs was found to accompany the differentiation of cerebellar interneurons. The extent of modification in cerebellar mRNA was determined to be much higher than the consequent changes in the composition of cerebellar proteins. We propose to use the ontogenetic variations in the levels of specific cerebellar mRNA species in normal and malformed cerebellum to identify proteins specific to particular types of cerebellar neurons.

Seasonal variability in fertilization and embryo quality rates in women undergoing IVF.

OBJECTIVE: IVF-ET provides unique controlled conditions for the study of seasonal influences on the human reproductive process. This study was designed to evaluate the effects of seasonality on fertilization rate, embryo quality, and conception rates. DESIGN: A retrospective observational cohort study. A chart review of all individuals undergoing IVF-ET from 1988 to 1991 at our institution was performed. SETTING: An assisted reproduction unit at a university-based tertiary medical center. PATIENT(S): 657 women, for a total of 1074 IVF-ET treatment cycles, were evaluated. From this population, we chose 305 women undergoing their first IVF-ET cycle for reasons of pure mechanical infertility. INTERVENTION(S): IVF-ET cycles. MAIN OUTCOME MEASURE(S): Seasonal variability in fertilization rates and quality-A embryo rates, and the correlation with the absolute number of light hours, as well as the influence of temperature, humidity, and other environmental parameters. RESULT(S): A significant seasonal variability in the fertilization rate and the quality-A embryo rate was demonstrated. The highest fertilization and quality-A embryo rates were observed during the spring and the lowest in the autumn. These changes correlated with the absolute number of light hours and its increment over time, but not with the temperature, humidity, or other environmental parameters. CONCLUSION(S): Seasonality seems to have a significant influence on the fertilization process and on the quality of the human embryos that are obtained in vitro, possibly because of the light/dark variations over time. If this finding is confirmed, these seasonal changes should be taken into account when evaluating infertility data and in everyday clinical practice.

The efficacy and safety of zona pellucida drilling by a 193-nm excimer laser.

OBJECTIVE: To examine the efficiency of argon fluoride excimer laser drilling of the zona pellucida of mouse oocytes in improving in vitro fertilization (IVF) at low sperm concentrations and to assess its safety. DESIGN: Oocytes obtained from (Balb/c x C57BL6)CB6F1 female mice were drilled by laser and divided into two groups: group I (89 oocytes) were inseminated with 10(5) sperm cells/mL, and group II (94 oocytes) were inseminated with 10(6) sperm cells/mL. Both groups' fertilization rate and development in vitro was compared with control oocytes that underwent the same preparation steps but no drilling (94 and 88 oocytes for group I and group II, respectively). MAIN OUTCOME MEASURES: The fertilization rate and the development in vitro of the laser-drilled groups is compared with that of the control. In addition, in vivo development of embryos generated from laser-drilled oocytes after transfer to pseudopregnant recipients is assessed. RESULTS: For both sperm concentrations, laser drilling significantly enhanced fertilization over control (67% versus 31% at 10(5) sperm cells/mL and 90% versus 54% at 10(6) sperm cells/mL). The development into the blastocyst stage after 96 hours of incubation was similar for both the laser-drilled and control groups at any sperm cell concentration. However, complete hatching at this point was significantly enhanced by the drilling procedure. Normal litters were obtained from the transfer of embryos developed from zona-drilled oocytes into pseudopregnant recipients. CONCLUSIONS: Excimer laser drilling enhanced IVF at low sperm cell concentration. The procedure is safe and did not interfere with embryo development in vitro or in vivo.

Helicoid peripapillary chorioretinal degeneration.

Study of a father and son who had helicoid peripapillary chorioretinal degeneration suggests that a progressive tearing and retraction of the retinal pigment epithelium or of Bruch's membrane around the optic disk may be involved in the disorder's pathogenesis. We presume that this tearing results primarily from dysplastic abnormalities of the retinal pigment epithelium that surrounds the optic disk. The dystrophic lesions progress slowly and may affect the macula and even the peripheral retina.

Multiple evanescent white dot syndrome after hepatitis B vaccine.

PURPOSE: Hepatitis B vaccine has become an effective means of preventing complications of hepatitis B. However, it occasionally induces serious side effects. We report a case of multiple evanescent white dot syndrome (MEWDS) that occurred following hepatitis B vaccination. METHODS: A 23-year-old woman with a one-week history of progressive loss of vision in the left eye and bilateral photopsia was referred for examination. Her symptoms appeared 24 hours after a booster intramuscular injection of hepatitis B vaccine. RESULTS: Clinical examination, fluorescein angiography, and the course of events were typical of MEWDS. CONCLUSIONS: This case demonstrates the occasional occurrence of MEWDS after hepatitis B vaccine and suggests that hepatitis B virus immunization may be a risk factor for this retinal condition.

Macular reflexes in optic atrophy.

We investigated the annular reflex of the macula and the foveal reflex in 14 eyes with various degrees of optic atrophy by means of red-free fundus photographs. The patients ranged in age from 13 to 34 years (mean age, 25.9 years). We compared our observations with data obtained from 51 age-matched normal eyes. Optic atrophy was found to be associated with changes in the reflexes of the macular area. Alterations occurred in all eight eyes that had visual acuities of 20/50 or worse. Changes in the annular reflex of the macula were more significant in younger patients (less than or equal to 25 years of age) than in older patients. In the younger group, the annular reflex was blunt, distorted, and fragmented, and showed an irregular extension toward the foveal area, whereas in the old group it showed less specific attenuation. Fading of the foveal reflex was observed in both groups. Changes in the retinal reflexes of these patients result from alterations in the ganglion cell and nerve fiber layer and should be included among the signs of optic atrophy. They can help determine the extent of optic atrophy and can be useful clinical clues in children whose optic disks are difficult to examine. They should not be mistaken for signs of associated primary retinal disorders.