Ouabain effects on intracellular potassium activity and contractile force in cat papillary muscle.

The relationship between the positive inotropic and toxic effects of cardiac glycosides and their effects on intracellular ionic composition is incompletely defined. We measured intracellular potassium activity (alpha ik), extracellular potassium activity (alpha ek), resting potential, action potential duration, and contractile force at 32 degrees C in paired papillary muscles from feline right ventricles exposed to ouabain. Muscles used for electrophysiological measurements were quiescent except for isolated stimulation to confirm impalement and record action potential duration. Muscles used for contractile force measurements were quiescent except for 4-min periods when force was measured at a cycle length of 1,400 ms. Muscle length was adjusted to achieve 50% of maximal tension at this cycle length before each experiment. In four experiments, alpha ik and contractile force were measured in the same muscle. Alpha iK was measured with single and double-barrel K-sensitive electrodes. At 10 nM ouabain, action potential duration is prolonged. Among the concentrations tested, the threshold for a clear positive inotropic effect is 0.1 microM ouabain. The threshold for decrease in alpha iK, increase in alpha eK, and decrease in membrane potential is 1 microM, at which concentration toxic signs develop, including arrhythmias, aftercontractions, and alteration in the staircase response of contractile force to repetitive stimulation. Ouabain need not change alpha iK to effect positive inotropy in ventricular muscle, a relationship different from that reported between [K]i (intracellular potassium concentration) and positive inotropy. Higher ouabain concentrations, which others have shown to clearly inhibit active Na and K transport, are shown to upset intracellular potassium activity homeostasis and to consistently produce toxicity.

Reliability of brightness comparison testing in predicting afferent pupillary defects.

We tested the reliability of brightness comparison testing in predicting relative afferent pupillary defects (RAPDs) in 206 patients. For unselected patients, brightness comparison testing correctly predicted the RAPD in 62% of patients. For subgroups of patients with glaucoma and optic nerve lesions, correct predictions were made in 92% and 83% of patients, respectively. Sensitivity and specificity of brightness comparison testing with a 6-V test light were 85% and 49%, respectively. In subgroups of patients who are strongly suspected of having an RAPD but in whom pupillary testing is not possible, brightness comparison testing can reliably predict presence or absence of an RAPD.

Pyoderma gangrenosum involving the eyelid.

A 62-year-old man was seen with an ulcer of the left upper eyelid of two weeks' duration. Over the previous 40 years, similar ulcers had intermittently developed elsewhere on his skin and spontaneously resolved over several months leaving atrophic scars. A biopsy specimen of the eyelid lesion showed epidermal ulceration with acute inflammation and liquefactive necrosis of the underlying dermis. Microorganisms and vasculitis were not present. On the basis of the clinical history and a compatible biopsy specimen, the diagnosis of pyoderma gangrenosum was made. This is an uncommon, idiopathic, ulcerating skin disease that may also have ocular manifestations. Eyelid ulcers have not previously been reported, to our knowledge. The diagnosis is established by clinical history and exclusion of other causes of ulceration.

Ocular rosacea.

The demographic, clinical, and histopathologic characteristics of ocular rosacea are reviewed, with emphasis on examination of the skin in patients with external ocular disease. Since no single clinical or pathological hallmark of rosacea exists, a proposed point system for diagnosis is presented. Studies of pathogenesis reveal that no single unifying hypothesis accounts for all the expressions of ocular rosacea. Reports of treatment with tetracycline and other antibiotics demonstrate efficacy, although the mechanisms of action of these drugs are not known. More recently, other classes of drugs, including isotretinoin and hexachlorocyclohexane, have proven to be effective in dermatologic manifestations of rosacea, but effects on ocular manifestations are unknown.

Tear studies in ocular rosacea.

To determine whether tear pH in ocular rosacea was alkaline or acidic compared to normal, I studied tear pH measured by pH electrode or paper in 12 patients with rosacea without ocular manifestations, 23 patients with mild ocular manifestations, and nine patients with severe ocular manifestations. There was no diagnostically useful difference in tear pH between any of these groups and normal controls. Possible pitfalls include the effect of anesthetic eyedrops on tear pH, the effect of basal tear secretion, and discrepancies between electrode and paper measurements. Measurements by pH paper cannot be adjusted by an error constant to yield an equivalent electrode value. Treatment of active ocular rosacea with tetracycline for one month had no effect on tear pH in six patients.

Vitreous Hemorrhage complicating laser-induced chorioretinal anastomosis for central retinal vein occlusion.

PURPOSE: To report a severe complication of laser chorioretinal anastomosis for central retinal vein occlusion. METHOD: Case report. RESULTS: In the right eye of a 62-year-old woman with nonischemic central retinal vein occlusion, retinal neovascularization at the laser chorioretinal anastomosis site caused dense secondary vitreous hemorrhage. Vitreous hemorrhage prevented laser panretinal photocoagulation for subsequent iris neovascularization, necessitating vitrectomy surgery to clear the hemorrhage and allow the treatment. CONCLUSION: Laser chorioretinal anastomosis can result in severe vitreous hemorrhage and complicate efforts to manage later sequelae of central retinal vein occlusion.

Ocular rosacea in blacks.

In three black men (57, 64, and 61 years old) with the ocular manifestations of rosacea, the diagnosis was not initially suspected because the pathognomonic skin changes of rosacea were obscured by the skin hyperpigmentation. Ocular involvement ranged from blepharitis and conjunctival hyperemia to sight-threatening problems such as corneal neovascularization, thinning, ulceration, and perforation. Treatment with oral tetracycline and topical corticosteroids appeared to be as effective in these patients as in previously described white patients.

Asymmetric retinopathy in patients with diabetes mellitus.

We reviewed retrospectively the records of 57 diabetic patients with asymmetric retinopathy persisting for two years or more (mean, 4.8 years) to identify intraocular risk and protective factors for the development of proliferative retinopathy. For each patient in this series, the more severely affected eye had proliferative retinopathy and the fellow eye had either background diabetic retinopathy or no retinopathy. Branch vein occlusion (P = .016) was identified as a statistically significant risk factor for proliferative retinopathy and chorioretinal scarring (P = .031) was found to be a statistically significant protective intraocular factor. In 34 patients with long-standing asymmetric retinopathy, no intraocular risk or protective factors were identified.

An exploratory study of the safety, tolerability and bioactivity of a single intravitreal injection of vascular endothelial growth factor Trap-Eye in patients with diabetic macular oedema.

AIM: The aim of the study was to assess the safety and bioactivity of a single intravitreal injection of vascular endothelial growth factor (VEGF) Trap-Eye in subjects with diabetic macular oedema (DMO). METHODS: Five subjects with DMO, foveal thickness > or =250 microm measured by optical coherence tomography (OCT), and best-corrected visual acuity (BCVA) between 20/40 and 20/320, were enrolled. Each participant received a single intravitreal injection of 4.0 mg of VEGF Trap-Eye followed by a 6-week observation period. Outcome measures included safety and biological activity, including changes in BCVA and excess retinal thickness assessed by OCT. RESULTS: Injections of VEGF Trap-Eye were well tolerated with no ocular toxicity. One patient had an unrelated serious adverse event: hospitalisation for cellulitis of the left foot 27 days after injection of VEGF Trap-Eye. Median baseline BCVA was 36 ETDRS letters read at 4 m (not ETDRS visual acuity score; Snellen equivalent: 20/50) and median baseline excess central 1 mm foveal thickness (FTH) was 108 microm. At 4 weeks after injection, the median excess FTH was 59 microm and the median improvement in BCVA was nine letters. At 6 weeks after injection, four of the five patients showed improvement in excess FTH (median 74 microm; 31% reduction from baseline, p = 0.0625) and four of the five showed improvement in BCVA (median improvement of three letters). CONCLUSIONS: A single intravitreal injection of 4.0 mg of VEGF Trap-Eye was well tolerated and preliminary evidence of bioactivity was detected. These findings support additional studies investigating multiple injections of VEGF Trap-Eye in patients with DMO.

Posterior segment manifestations of active ocular syphilis, their response to a neurosyphilis regimen of penicillin therapy, and the influence of human immunodeficiency virus status on response.

OBJECTIVE: To determine the relative frequencies of signs in posterior segment ocular syphilis, the response to a neurosyphilis regimen of penicillin, and differences in findings between human immunodeficiency virus (HIV)-coinfected and -noncoinfected patients in a community setting. DESIGN: Retrospective, noncomparative, consecutive case series. PARTICIPANTS: Fourteen consecutive patients with posterior segment ocular syphilis over a 14-year period within or during the acquired immune deficiency syndrome era. INTERVENTION: Neurosyphilis intravenous penicillin regimen. MAIN OUTCOME MEASURES: Initial and final visual acuity; treponemal and nontreponemal serologic analyses; cerebrospinal fluid cell count, protein, and Venereal Disease Research Laboratory analyses; posterior segment signs; and relapses and recurrences. RESULTS: Blacks and males were predominantly affected. Five (36%) of patients were HIV coinfected, and ocular syphilis led to the HIV infection diagnosis in three. Four (29%) patients had received previous antibiotic therapy for primary or secondary syphilis, raising the suspicion of relapse. Two patients had negative nontreponemal serologic results. All patients responded rapidly to neurosyphilis therapy. One patient subsequently relapsed after neurosyphilis therapy, and a second was reinfected with recurrence of ocular involvement. One previously undescribed retinal manifestation was discovered: a sectorial retinochoroiditis with delayed retinal circulation in the involved area. CONCLUSIONS: Ocular syphilis is a form of neurosyphilis and requires neurosyphilis therapy regardless of when it develops after primary infection. Conventional syphilis staging is of little use in understanding ocular syphilis. A high suspicion for this diagnosis is appropriate, especially in poorer black males with posterior segment inflammatory disease. Human immunodeficiency virus coinfection with ocular syphilis is common, but does not affect response to a neurosyphilis regimen of penicillin in the short term. Awareness of the multiple presentations of posterior segment ocular syphilis will aid ophthalmologists in averting misdiagnosis or delayed diagnosis.

Fundus photographic, fluorescein angiographic, and indocyanine green angiographic signs in successful laser chorioretinal venous anastomosis for central retinal vein occlusion.

OBJECTIVE: To describe the fundus signs and angiographic signs that accompany development of a laser-induced chorioretinal venous anastomosis in central retinal vein occlusion and to describe the chronology of the signs. DESIGN: Noncomparative, consecutive case series. PARTICIPANTS: Fifteen eyes of 15 patients were treated. INTERVENTION: The argon laser was used in the original method of McAllister and Constable to form an anastomosis in five eyes, and the modified method of McAllister involving the argon laser followed by the YAG laser was used for ten eyes. MAIN OUTCOME MEASURES: Changes in vessel diameters, retinal blood flow, and morphology of anastomosis over time as documented photographically and angiographically. RESULTS: The earliest fluorescein angiographic sign of success is a hyperfluorescent spindle at 1 week. The earliest indocyanine green angiographic sign is direct connection of retinal venous and choroidal venous circulations at 2 weeks. The earliest fundus photographic and, hence, ophthalmoscopic sign is asymmetry in venous diameter at the disc at 3 weeks. No sign is present in all successful cases. The most commonly observed sign is fluorescein flow around a corner in a retrograde direction toward the anastomosis in 80% of cases. Drainage of only a fraction of the retina occurred in 93% of cases. Fifteen eyes with successful anastomoses had mean improvement of 2.3 +/- 2.4 (standard deviation [SD]) Snellen lines of best-corrected visual acuity compared to 0.2 +/- 2.3 (SD) lines for 9 eyes with unsuccessful anastomoses (P = 0.0439). CONCLUSION: Recognition of the variety and typical chronology of postoperative fundus and angiographic signs in laser-induced chorioretinal anastomosis will help prevent premature retreatment and guide appropriately timed additional treatment for failed initial attempts. Fluorescein angiography and indocyanine green angiography are necessary components of intensive postoperative follow-up of these patients. The follow-up care is more difficult than the technical aspects of the surgery itself. Successful anastomoses help by taking part of the flow away from the compromised central vein, not by providing global venous bypass. This technique remains controversial, unproven, and in need of a randomized clinical trial to determine its role in the management of nonischemic central retinal vein occlusion.

The test light affects quantitation of the afferent pupillary defect.

Nineteen patients with afferent pupillary defects (APDs) from a variety of lesions were examined using a brighter and dimmer test light. A denser neutral density filter was required to balance the afferent defect using the brighter test light in every case. For quantitation of an afferent defect to have meaning, the test light used must be specified. An indirect ophthalmoscope set to 6 V and held 1 foot from the eyes will allow easier detection of subtle relative APDs than it will if set to 3 V.

Effects of stimulation frequency on potassium activity and cell volume in cardiac tissue.

We examined the effects of increases in stimulation frequency on the intracellular potassium activity and cell volume of feline and canine Purkinje fibers and feline ventricular fibers. Intracellular potassium activity was measured with potassium liquid ion exchanger microelectrodes in single- and double-barrel configuration. Cell volume was measured with an electrophysiologic technique. From single-barrel electrode recordings, intracellular potassium activities (means +/- SE) in feline Purkinje fiber, feline papillary muscle, and canine Purkinje fiber are 117.1 +/- 5.4, 87.3 +/- 3.1, and 112.4 +/- 4.4 mM, respectively, with [K]o (external potassium concentration) of 5.4 mM. Thus direct evidence for a 30-mM gradient in intracellular potassium activity from Purkinje fiber to ventricular muscle is presented. Intracellular potassium activity did not change in any tissue studied during or after 3 min of 4 Hz stimulation. The lack of change is partially explained by a reversible 2% decrease in cell volume induced by the stimulation protocol. Net losses greater than 2% seen in earlier studies probably reflect either differences between perfused vs. superfused preparations or functional sequestration of cellular potassium involved in transfers during frequency changes.

The effect of the surgeon and the laser wavelength on the response to focal photocoagulation for diabetic macular edema.

OBJECTIVE: To determine the effect of the surgeon and the wavelength of laser used on the response to focal photocoagulation for diabetic macular edema. DESIGN: Retrospective case-control study. PARTICIPANTS: Forty-four matched pairs of cases by two different retina surgeons in the study of surgeon influence were examined. Sixty-nine matched pairs of cases using dye yellow versus argon green laser treatment in the study of wavelength influence also were studied. In both studies, eyes were matched for the only patient-dependent variables affecting outcome: age, initial visual acuity, follow-up time, and diabetic control by diet versus any other method. INTERVENTION: Focal laser photocoagulation for clinically significant diabetic macular edema was performed. MAIN OUTCOME MEASURE: Visual acuity at 6 months follow-up was measured. RESULTS: For the study in which the only difference was the surgeon, at 6 months follow-up the mean difference in logarithm of the minimum angle of resolution (logMAR) visual acuity was -0.045, 95% confidence interval (-0.160, 0.070). For the study in which wavelength varied, at 6 months the mean difference in logMAR visual acuity was -0.048, 95% confidence interval (-0.147, 0.052). The power of the surgeon study to detect a difference in the logMAR visual acuity of 0.3 is 88% and of the wavelength study to detect this difference is 99%. CONCLUSION: In looking at the 6-month visual outcome after focal laser photocoagulation for clinically significant diabetic macular edema, different fellowship trained surgeons and the choice of green or yellow wavelength had no effect on the treatment outcome.

Laser chorioretinal venous anastomosis for nonischemic central retinal vein occlusion.

OBJECTIVE: This study aimed to test the efficacy and safety of laser chorioretinal anastomosis for central retinal vein occlusion (CRVO). DESIGN: The study design was a consecutive case series. PARTICIPANTS: Eight eyes of eight patients were treated. INTERVENTION: The argon laser was used in the method of McAllister and Constable to attempt to form an anastomosis. The patients were observed for 1 to 19 months (median, 11 months). MAIN OUTCOME MEASURES: Visual acuity, anastomosis success, and complications were measured. RESULTS: Twenty attempts to create anastomoses were made with 2 successful anastomoses but not of a therapeutic type. Three patients developed rubeosis, retinal neovascularization at the laser site, and vitreous hemorrhage. Traction retinal detachment occurred twice and neovascular glaucoma occurred once. Secondary panretinal photocoagulation, pars plana vitrectomy, and glaucoma seton were required in three patients, one patient, and one patient, respectively. Visual acuity improved in two patients independent of failed attempts at anastomosis creation and did not improve or worsened in six patients, including the two patients with the successfully created anastomoses. CONCLUSION: Laser chorioretinal anastomosis for nonischemic CRVO has greater risks and less success than the initial report suggested. Further refinement of the technique is needed before it is adopted extensively. Even when successful, macular pigment epithelial scarring can limit vision, implying a relatively short time window for its effective application in the face of severe macular edema. Successful laser chorioretinal anastomosis does not preclude development of anterior segment neovascularization.

Early experience in extracapsular cataract surgery by residents.

We studied retrospectively the problems encountered by residents learning extracapsular cataract surgery and the variables influencing visual outcomes and complications in 130 patients. Although visual results were comparable to reported series by experienced surgeons, rates of complications were higher with 9% vitreous loss and 17% posterior capsule rupture in the first 25 cases of the average resident's experience. A learning curve depicting when complications occur shows that learning to avoid vitreous loss is a much faster process than learning to avoid posterior capsule rupture. Inter-resident variability in prevalence of complications was large. The axis of postoperative astigmatism was not consistent in residents at this stage of experience. Residents are not accurate judges of the effect faculty attendings have on visual outcomes and complication rates.