Long-Term Efficacy and Safety of Tretinoin Emollient Cream 0.05% in the Treatment of Photodamaged Facial Skin

Background: Long-term (>1 year) placebo-controlled studies of tretinoin in the treatment of photodamaged skin have not been conducted. Recently, we conducted a 2-year placebo-controlled study of tretinoin emollient cream 0.05%, including histopathologic assessment of safety and analysis of markers of collagen deposition. Objective: The objective of the study was to determine the long-term safety and efficacy of tretinoin emollient cream 0.05% in the treatment of moderate to severe facial photodamage. Methods: A total of 204 subjects were treated with tretinoin or placebo (vehicle emollient cream) applied to the entire face once a day for up to 2 years. Clinical and histologic effects were assessed at regularly scheduled clinic visits. Results: Treatment with tretinoin resulted in significantly greater improvement relative to placebo in clinical signs of photodamage (fine and coarse wrinkling, mottled hyperpigmentation, lentigines, and sallowness), overall photodamage severity, and investigator’s global assessment of clinical response (p < 0.05). Histologic evaluation showed no increase in keratinocytic or melanocytic atypia, dermal elastosis, or untoward effects on stratum corneum following treatment with tretinoin compared with placebo. Immunohistochemistry studies, conducted at three study centers, showed a significant increase relative to placebo in facial procollagen 1C terminal, a marker for procollagen synthesis, at month 12 (p = 0.0074). Conclusion: Long-term treatment with tretinoin emollient cream 0.05% is safe and effective in subjects with moderate to severe facial photodamage.     

Age-related changes in sympathetic neurotransmission in rat retina and choroid

While age-related night vision loss and age-related macular degeneration are well characterized, less is known about the normal aging process in the retina and choroid. The purpose of this study was to ascertain whether dopamine beta-hydroxylase (DBH), beta1- and beta2-adrenergic receptor gene and protein expression are altered in the retina and choroid with age. The retina and choroid were dissected from F344xBNF1 hybrid rats aged 8, 22, and 32 months. Real-time PCR and Western blot analysis were conducted to determine steady-state mRNA and protein expression. Immunohistochemistry (IHC) was conducted to localize DBH protein expression in the retina. DBH protein expression was substantially decreased with age in the retina, particularly in the outer nuclear layer, with no changes in DBH expression noted in the choroid. There was a significant increase in beta1-adrenergic receptor protein expression in retinal samples at 22 months, while beta2-adrenergic receptor protein expression was not affected by age. Decreased expression of DBH with age in the retina could lead to reduced production of norepinephrine, potentially resulting in an increase of beta1-adrenergic receptor expression due to denervation supersensitivity. Gene expression for DBH, beta1- and beta2-adrenergic receptors were observed to peak at 22 months and return to baseline levels by 32 months of age in the choroid. Our findings suggest that the retina may be more sensitive to age-related loss of sympathetic neurotransmission than the choroid, which may partially explain normal age-related vision loss in the elderly.     

Monitoring glaucomatous visual field progression: the effect of a novel spatial filter

PURPOSE: To assess the impact of a novel visual field spatial filtering technique on the detection of glaucomatous progression. METHODS: One hundred ninety-eight ocular hypertensive (OHT) and 21 control subjects were examined prospectively (1994-2001) with regular full-threshold Humphrey visual field (VF) testing. VF progression was assessed by point-wise linear regression (PLR) of sensitivity/time in Progressor for Windows software modified to include a novel spatial filter. Standard progression criteria (slope > -1 dB/year, P < 0.01) were applied to both "raw" (unfiltered) and "filtered" VF series. Three-omitting confirmatory VF criteria were also applied to unfiltered VF series. Specificity was estimated as the proportion of progressing control subjects and as the proportion of significantly improving subjects (both OHT and control) at the end of the study period. RESULTS: Applying standard PLR, specificity was estimated at 91.8% to 97.5% using unfiltered standard PLR, compared with 93.5% to 98.4% using filtered standard PLR and 95.4% to 99.3% using unfiltered three-omitting PLR. The rate of identified VF progression in the OHT cohort was 32.3% with unfiltered standard PLR, 28.7% with filtered standard PLR, and 18.6% with unfiltered three-omitting PLR. There was no significant difference in time to detected progression between filtered and unfiltered standard PLR. CONCLUSIONS: The use of confirmatory tests resulted in improved specificity using unfiltered data; however, application of the spatial filter resulted in similar specificity but with a higher rate of detected progression. This filter may therefore be useful in the monitoring of glaucomatous progression as it may reduce the dependence on confirmatory testing, although it has yet to be applied to longitudinal SITA data.     

Induction of axon and dendrite formation during early RGC-5 cell differentiation

The retinal ganglion cell (RGC)-like RGC-5 line can be differentiated with staurosporine to stop dividing, extend neurites, and increase levels of several ganglion cell markers. This allows study of regulation of neurite development on a single cell basis. However, it is unclear whether the neurites induced by differentiation have features characteristic of dendrites or axons. To address this question, RGC-5 cells were differentiated with staurosporine and then immunoblotted for microtubule-associated protein 2 (MAP2) and actin, or stained immunocytochemically for different MAP2 isoforms, tau, growth-associated protein 43 (GAP-43), or the neuronal marker beta-III-tubulin. We found that staurosporine-induced differentiation led to an upregulation of MAP2c, a MAP2 isoform expressed in developing neurons. Some neurites expressed MAP2c but not the dendritic markers MAP2a and MAP2b, consistent with an axonal phenotype. Some neurites expressed the axonal marker tau in a characteristic proximal-to-distal gradient, and had GAP-43 labeling characteristic of axonal growth cones. The presence of MAP2c in differentiated RGC-5 cells is indicative of RGC-like neurite development, and the pattern of staining for the different MAP2 isoforms, as well as positivity for tau and GAP-43, indicates that differentiation induces axon-like and dendrite-like neurites.     

Retinotopic organization of primary visual cortex in glaucoma: a method for comparing cortical function with damage to the optic disk

PURPOSE: To demonstrate that the relationship between the functional organization of primary visual cortex (V1) and damage to the optic disc in humans with primary open-angle glaucoma (POAG) can be measured using a novel method for projecting scotomas onto the flattened cortical representation. METHODS: Six subjects participated in this functional magnetic resonance imaging (fMRI) experiment. Structural damage to the optic disc and the retinal nerve fiber layer (RNFL) was measured by three techniques: scanning laser polarimetry (GDx ECC; Carl Zeiss Meditec, Dublin, CA), confocal scanning laser ophthalmoscopy (HRT II; Heidelberg Engineering, Heidelberg, Germany), and optical coherence tomography (StratusOCT; Carl Zeiss Meditec, Inc.). Cortical activity for viewing through the glaucomatous versus fellow eye was compared by alternately presenting each eye with a contrast-reversing checkerboard pattern. The resultant fMRI response was compared to interocular differences in RNFL or mean height contour for analogous regions of the visual field. RESULTS: fMRI responses to visual stimulation were related to differences in RNFL thickness or mean height contour between eyes. The correlation between fMRI responses and measurements of optic disc damage for OCT (RNFL), HRT (mean height contour), and GDx (RNFL) were r = 0.90 (P = 0.02), r = 0.84 (P = 0.04), and r = 0.79 (P = 0.063), respectively. The probability of observing all three correlations by chance was low (P = 0.0003). CONCLUSIONS: Cortical activity in human V1 was altered in these six POAG subjects in a manner consistent with damage to the optic disc. fMRI is a possible means for quantifying cortical neurodegeneration in POAG.     

Complications in resident-performed phacoemulsification cataract surgery at New Jersey Medical School

AIM: To describe the complications related to cataract surgery performed by phacoemulsification technique by third-year ophthalmology residents at New Jersey Medical School, who are trained to perform phacoemulsification without any prior experience with extracapsular extraction. DESIGN: Retrospective, observational case series. METHODS: A retrospective chart review of 755 patients who underwent cataract surgery by third-year residents between July 2000 and June 2005 at the Institute of Ophthalmology and Visual Science was performed. Details of intraoperative complications (posterior capsular rupture, vitreous loss, subluxation of lens fragments into the vitreous, extracapsular cases converted to phacoemulsification, retinal detachment, vitreous haemorrhage and haemorrhagic choroidals) of the cases done by phacoemulsification technique were recorded. Results were analysed and compared with complication rates reported from other residency programmes and from experienced ophthalmologists. RESULTS: Of 755 cataract surgeries, 719 were performed using phacoemulsification technique. Posterior capsule disruption occurred in 48 (6.7%), vitreous loss in 39 (5.4%) and dislocated lenticular fragments in 7 (1.0%) of 719 cases that underwent phacoemulsification technique. Subsequent pars plana lensectomy was required in 5 (0.7%) cases; 1 case (0.1%) experienced retinal detachment and haemorrhagic choroidal detachment. CONCLUSION: The residents can perform phacoemulsification well with a very low complication rate, without prior training with extracapsular cataract extraction technique.     

Neurohistology of lumbar spine ligaments

A study was conducted to identify neural elements in the posterior ligaments of the lumbar spine by using a modified gold-chloride method. Three morphologic types of mechanoreceptors were identified: Ruffini corpuscles, Ruffini end organs, and pacinian corpuscles. Free nerve endings, which are thought to be responsible for pain production, were also demonstrated within the ligaments.     

Coronary artery disease in aortic surgery

The incidence of coronary artery disease in patients coming to aortic surgery and the impact of aggressive preoperative cardiac catheterization and myocardial revascularization was prospectively analyzed in 59 patients. Seventy-five percent of patients had at least one-vessel involvement, and 32% had three-vessel or left main involvement. Patients with electrocardiographic evidence of coronary artery disease had at least one-vessel involvement 84% of the time and three-vessel, left main involvement 36% of the time. Sixty-four percent of patients with no preoperative indications of coronary artery disease had at least one-vessel involvement and 29% had three-vessel, left main involvement. Resting (39 patients) and exercise multiple-gated acquisition scans (22 patients) did not predict the presence of coronary artery disease in patients without a history or electrocardiographic evidence of coronary artery disease. Myocardial revascularization was performed prior to aortic surgery in 17 patients (29%). The operative mortality was 3.7% with two patients dying from noncardiac-related complications. There were two additional deaths prior to aortic surgery with one patient dying during coronary artery bypass grafting, and one dying of aneurysm rupture prior to repair, making the overall mortality associated with this approach 7.4%. Preoperative cardiac catheterization and an aggressive approach toward coronary artery bypass grafting reduces the risk of cardiac complications in aortic surgery.