Delays in rod-mediated dark adaptation in early age-related maculopathy.

OBJECTIVE: To determine whether there are disturbances in the rod-mediated kinetics of dark adaptation in early age-related maculopathy (ARM). DESIGN: Comparative, observational case series. PARTICIPANTS: Twenty older adults with early ARM as defined by one or more large (> 63 microm) drusen, focal hyperpigmentation, or both, but no choroidal neovascularization or geographic atrophy, and 16 adults in the same age range with none of these fundus features. All participants had 20/25 visual acuity or better in the tested eye. METHODS: Dark adaptation functions were measured using a modified Humphrey Field Analyzer (Zeiss Humphrey Systems, Dublin, CA) to assess the rate of rod-mediated sensitivity recovery at 12 degrees on the vertical meridian in the inferior visual field after exposure to the equivalent of a 98% bleach. Baseline (prebleach) scotopic sensitivity, visual acuity, contrast sensitivity, and photopic sensitivity were also measured. MAIN OUTCOME MEASURES: Rod-cone break; second and third components of rod-mediated dark adaptation; time to baseline sensitivity; and baseline (prebleach) scotopic sensitivity. RESULTS: Although their visual acuity was at least 20/25, patients with early ARM on average exhibited deficits in almost all rod-mediated parameters of dark adaptation as compared with age-similar healthy participants. For example, the rod-cone break was delayed approximately 10 minutes in early ARM patients as compared with healthy participants. Age-related maculopathy patients were more likely to fall outside the normal reference range for variables representing dark adaptation kinetics than for steady-state visual functions such as scotopic sensitivity. For example, 85% of ARM patients fell outside the normal reference range in at least one dark adaptation kinetic parameter, whereas only 25% of ARM patients fell outside the normal reference range for steady-state scotopic sensitivity. CONCLUSIONS: Rod-mediated kinetic parameters of dark adaptation, which reflect the sensitivity recovery of the visual cycle, are disrupted early in ARM pathogenesis.

Tractional force generation by porcine Müller cells: stimulation by growth factors in human vitreous.

PURPOSE: To examine the levels of Müller cell contraction-stimulating activity in human vitreous, correlate these levels with clinical presentation, and identify, the causative growth factors. METHODS: Human vitreous was collected from patients undergoing pars plana vitrectomy (n = 84). Müller cells were isolated from porcine retina and maintained in tissue culture. Tractional forces generated by cells incubated on three-dimensional collagen gels were measured as changes in gel thickness. Contraction-stimulating activity in vitreous (VA) was calculated from the close-response profiles of gel contraction to vitreous protein. The contributions of individual growth factors to vitreous activity (n = 10) were assessed by inhibition with specific neutralizing antibodies. RESULTS: The mean VA of patients with retinal detachment (3.65) and proliferative vitreoretinopathy stages A, B, and C (2.06) were elevated above that of patients without retinal pathology (vitreous activity = 0.23) or retinal defects alone (0.57). Mean activities in patients with epimacular proliferation (1.22) and vitreous hemorrhage (1.40) were also significantly elevated. The percentage of this activity attributable to insulin-like growth factor 1 (IGF-1) varied from 9.2% to 84.5% with a mean of 61.3%. Similarly, the percent contribution of platelet-derived growth factor (PDGF) ranged from 6.8% to 49.0% with a mean of 26.5%. CONCLUSIONS: The vitreous of patients with retinal detachment, proliferative retinal disease, and vitreous hemorrhage contain varying amounts of growth factors that stimulate tractional force generation by Müller cells. The majority of the activity can be attributed to IGF-1 and a smaller proportion to PDGF.

Search for impact remains at the Frasnian-Famennian boundary in the stratotype area, southern France.

In order to detect whether the end-Frasnian worldwide biotic crisis is related to an extraterrestrial impact, the global stratotype section of the Frasnian-Famennian boundary and auxiliary sections within the stratotype area have been examined for impact indicators: iridium. Ni-rich spinel bearing spherules and glassy microtektites. This area is particularly well suited to the search for discrete events because it exhibits biostratigraphically continuous sections of sedimentologically homogenous off-shore deposits. Different environmental settings on oxygenated deep-water seamounts, such as the stratotype section at Coumiac, and in oxygen-depleted depressions (La Serre section) are available. The latter is investigated in more detail because it is the least condensed across the boundary, which is determined by the first occurrence of the typical morphotype of Palmatolepis triangularis, the indicator of the first Famennian conodont biozone. Samples from the biostratigraphically defined boundary and adjacent levels failed to provide significantly high Ir values and no Ni-rich spinel or microtektite has been recovered. This is in contradiction with the results of earlier investigations carried out by H. Geldsetzer on the same section. In contrast, the values of Ir concentrations that we measured are always very low or not detectable. The small overabundances observed in some samples, which are about two orders of magnitude lower than what is currently observed at the Cretaceous-Tertiary boundary, are probably due to the accumulation of the normal flux of cosmic dust during periods of relatively low depositional rates or to a terrestrial origin. At present, we have no evidence that an extraterrestrial impact occurred at the F-F transition.

Microholes of the macula.

OBJECTIVE: To describe the clinical syndrome of microholes of the macula. PATIENTS: Fourteen patients with acute symptoms caused by full-thickness microholes of the macula. RESULTS: Patients with macular microholes had the acute onset of central scotoma with mild to moderate visual acuity loss. Examination revealed a detachment of the vitreous over the fovea, often with an operculum or a total posterior vitreous detachment, and a sharply demarcated, 50- to 133-micrometer round hole in the center of the macula. On follow-up, all patients had a stable or improved scotoma and visual acuity. CONCLUSIONS: Macular microholes appear to be caused by an acute detachment of the vitreous from the fovea and can be distinguished from Gass stage 2 idiopathic macular holes.

Pathologic human vitreous promotes contraction by fibroblasts. Implications for proliferative vitreoretinopathy.

OBJECTIVE: To establish and quantify the presence of contraction-stimulating activity in pathologic vitreous and correlate this activity with clinical presentation and outcome, especially with proliferative vitreoretinopathy. METHODS: Contraction-stimulating activity of vitreous collected during surgery was quantified with a tissue culture assay using fibroblasts as target cells. The activity of each sample was correlated with patient history, clinical presentation, risk factors, proliferative disease, and postoperative proliferation. RESULTS: Pathologic vitreous contained measurable quantities of contraction-stimulating activity and stimulated contraction in vitro, with elevated activities in samples from patients with proliferative vitreoretinopathy, epimacular proliferation, retinal detachment, retinal defects, pigmented cells in the vitreous, hemorrhage, or uveitis. Patients with postoperative proliferation had significantly elevated mean activities. CONCLUSIONS: Levels of contraction-stimulating activity in pathologic vitreous correlate with some risk factors for the development of proliferative vitreoretinopathy and may ultimately be useful in the assessment of disease severity and the prediction of postoperative proliferation.

Effectiveness of apraclonidine and acetazolamide in preventing postoperative intraocular pressure spikes after extracapsular cataract extraction.

We studied the effectiveness of two prophylactic agents in controlling early postoperative intraocular pressure (IOP) increases after cataract surgery. Fifty-four nonglaucomatous patients received either topical 1% apraclonidine, one drop before and after surgery, or sustained-release acetazolamide, 500 mg, or no medication at the completion of planned extracapsular cataract extraction (ECCE). Mean baseline IOPs were similar among patients randomized to the apraclonidine, acetazolamide, and control groups: 15.29 mm Hg, 15.33 mm Hg, and 14.26 mm Hg, respectively. At 3 hours postoperatively, IOPs were significantly lower in the apraclonidine group (11.13 mm Hg, P = .035), nonsignificantly lower in the acetazolamide group (13.3 mm Hg, P = .17), and significantly increased in the control group (21.32 mm Hg, P = .003). One eye in the apraclonidine group and six in the control group had IOPs greater than 30 mm Hg. At 24 hours, the only statistically significant difference was in the control group, whose mean IOPs remained elevated (21.83 mm Hg, P = .0008). One eye in the apraclonidine group, two in the acetazolamide group, and five in the control group had IOPs greater than 30 mm Hg. We found a significant early IOP reduction with apraclonidine given topically preoperatively and at the completion of planned ECCE.

Intraocular dexamethasone penetration via subconjunctival or retrobulbar injections in rabbits.

Using high-performance liquid chromatography, we compared tissue levels of dexamethasone in the aqueous, vitreous, retina, and choroid of rabbits, 1 and 4 hours following subconjunctival or retrobulbar injection. One hour following injection, dexamethasone levels in all of these tissues were similar in both the subconjunctival and retrobulbar groups. Four hours following injection, the concentrations in the two groups also were similar, except in the choroid, in which the subconjunctival injection yielded significantly lower dexamethasone levels than the retrobulbar injection. Tissue steroid levels were comparable ipsilateral and contralateral to the injected eyes in both treatment groups after 4 hours, except in the retina, in which the levels were lower in the contralateral eye after subconjunctival injection. These data suggest that dexamethasone absorption and delivery is predominantly hematogenous following both subconjunctival and retrobulbar injection, especially in highly vascular tissues, such as the choroid. Hematogenous delivery of dexamethasone appears to peak earlier in the choroid and presumably in other intraocular tissues following subconjunctival injections, while retrobulbar injections provide more steady, long-term delivery.

Branch retinal vein occlusion and quadratic variation in arteriovenous crossings.

To explore further the origin and clinically observed regional variation of branch retinal vein occlusion, we studied fluorescein angiograms of 42 patients (42 eyes) with branch retinal vein occlusion and a control population of 126 consecutive patients. In a statistically significant percentage of crossings, the artery was anterior to the vein in those areas of the retina clinically predisposed to branch retinal vein occlusion. Thirty-nine of the 42 patients with branch retinal vein occlusion sites had artery-anterior-to-vein crossings (P = .002), whereas 183 of all 266 arteriovenous crossings in these same eyes were similarly positioned. The artery lay anterior to the vein in significantly more temporal retinal crossings (337 of 457) than nasal retinal crossings (89 of 149; P = .002). Similarly, significantly more superotemporal quadrant crossings (164 of 209) than inferotemporal quadrant crossings (173 of 248) had the artery anterior to the vein (P = .0045). These results suggested that variation in the pattern of arteriovenous crossings may have a role in the clinical distribution of branch retinal vein occlusion.

Nondetectable electroretinogram in combined methylmalonic aciduria and homocystinuria.

We present the case of a patient with congenital methylmalonic aciduria with homocystinuria and a nondetectable electroretinogram. To our knowledge, this is a new entity to be considered in the differential diagnosis of nondetectable electroretinography in infancy.

Intravitreal U75412E: a new free radical scavenger.

Free-radical-mediated tissue damage is thought to be involved in a multitude of ophthalmic pathologies. Therefore, drugs that scavenge free radicals may find wide clinical application. A new chemical class of antiinflammatory agents, the 21-aminosteroids, has been developed as free radical scavengers. These agents are thought to inhibit lipid peroxidation and prevent the release of free arachidonic acid from injured cell membranes. In the present study, we investigated the intraocular toxicity of one of the 21-aminosteroids, U75412E. Intravitreal doses of up to 0.1 mg of U75412E were nontoxic to rabbit ocular tissues.

Orbital and sinus inflammation with secondary optic neuropathy.

Optic neuropathy with simultaneous orbital and sinus inflammation is a diagnostic dilemma. Although sinus inflammation was described previously as causative in some cases of optic neuritis, the relatively high rate of asymptomatic sinus opacification in radiologic studies of the general population (as high as 13%) makes this a diagnosis of exclusion. We describe a patient who had optic neuropathy associated with simultaneous orbital and sinus inflammation. Although definitive determination of etiology may not be made without tissue biopsy, cases suspected of having a bacterial etiology may benefit from an initial 48-hour trial of intravenous antibiotics before initiation of systemic corticosteroids.

Penetrating ocular injury from contaminated eating utensils.

Although the rate of infectious endophthalmitis following penetrating ocular injury is generally less than 10%, certain settings may carry a greater risk of infection. One such setting is penetrating injury resulting from eating utensils contaminated with oral flora. We reviewed six of these injuries. Culture-positive bacterial endophthalmitis developed in four of the six eyes; only one of the eyes retained reading visual acuity (greater than 20/50) and two eyes lost light perception. The potential for infection and limited visual outcome in this series warrants aggressive prophylaxis and treatment. The unexpected isolation of Haemophilus influenzae in two of the four infections suggests that broad-spectrum antibiotic treatment should be considered in all such injuries since less common organisms may be encountered.

Haptic externalization in a backwardly placed anterior chamber intraocular lens.

A patient who had been asymptomatic following extracapsular cataract extraction with posterior capsule rupture and anterior chamber lens implantation presented 18 months postoperatively with iritis and erosion of the superior haptic through the site of the cataract wound. At the time of explantation, it was seen that the anterior chamber lens had been inserted in a backward manner with the anterior face of the lens placed posteriorly. The resultant lens vaulting placed the superior haptic in the same plane as the cataract wound. Whether the superior haptic had initially been incorporated in the surgical wound or had eroded through the eye wall from the anterior chamber, the backward placement of the anterior chamber lens likely played a role in the development of haptic externalization.

Vitrectomy in asteroid hyalosis.

Asteroid hyalosis (AH), a condition in which calcium-lipid complexes form in the collagen meshwork of the vitreous, affects from 0.5% to 0.9% of the general population. In patients with dense AH and visual loss, obscuration of fundus detail on ophthalmoscopy and even on fluorescein angiography may complicate the diagnosis and treatment of underlying posterior segment disease. To evaluate the usefulness of vitrectomy in AH, we reviewed 7 cases of dense AH in 6 patients who underwent vitrectomy in the setting of decreased visual acuity of uncertain cause. Additional diagnoses made following surgery included age-related macular degeneration (ARMD) in 2 eyes, ARMD with associated epiretinal membrane in one eye, and the staging of diabetic retinopathy as proliferative in one eye. Although no major surgical complications occurred in this series, the potential for serious complications exists, and pars plana vitrectomy (PPV) should be considered only after less invasive diagnostic evaluations and therapeutic approaches have been exhausted.

Ocular self-mutilation.

A 32-year-old paranoid schizophrenic man repeatedly stabbed both his eyes with a sharpened wire coat hanger. The patient underwent vitrectomy on each eye approximately 2 1/2 weeks after injury, with multiple retinal defects noted OU. None of the posterior wounds involved the macula or optic disc, and final vision was 20/70 OD and 20/50 OS. Ocular self-mutilation, deliberate and severe self-injury which threatens visual function, is a rare occurrence most often described in acutely psychotic patients. Psychosis may be due to schizophrenia, drug abuse, manic phases of bipolar mood disorders, and depression. A striking number of these patients have delusions with religious and sexual content. They are prone to repeated attempts during the acute psychotic phase and must be monitored closely at this time.