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Biomedical subjects

Paul R Lichter

Publications and source records attributed to Paul R Lichter.

14 recordsLinked to original sources
PubMed2006

Implantable miniature telescope for the treatment of visual acuity loss resulting from end-stage age-related macular degeneration: 1-year results.

PURPOSE: To evaluate the safety and efficacy of an implantable visual prosthetic device (IMT; VisionCare Ophthalmic Technologies, Saratoga, CA) in patients with bilateral, end-stage age-related macular degeneration (AMD). DESIGN: Prospective, open-label, multicenter clinical trial with fellow eye controls. PARTICIPANTS: A total of 217 patients (mean age, 76 years) with AMD and moderate to profound bilateral central visual acuity loss (20/80-20/800) resulting from bilateral untreatable geographic atrophy, disciform scars, or both were enrolled. METHODS: A visual prosthetic device (implantable telescope), designed to enlarge retinal images of the central visual field, was implanted monocularly in the capsular bag after lens extraction. Fellow eyes were not implanted to provide peripheral vision and served as controls. Study patients participated in 6 visual rehabilitation visits after surgery. MAIN OUTCOME MEASURES: Best-corrected distance visual acuity (BCDVA) and best-corrected near visual acuity (BCNVA), quality-of-life scores from the National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) and the Activities of Daily Life scale, endothelial cell density (ECD), and incidence of complications and adverse events. RESULTS: At 1 year, 67% of implanted eyes achieved a 3-line or more improvement in BCDVA versus 13% of fellow eye controls (P<0.0001). Fifty-three percent of implanted eyes achieved a 3-line or more improvement in both BCDVA and BCNVA versus 10% of fellow eyes (P<0.0001). Mean BCDVA and BCNVA improved 3.5 lines and 3.2 lines, respectively, in implanted eyes versus 0.8 lines and 1.8 lines, respectively, in fellow eyes (P<0.0001). Change in visual acuity was not related to lesion type. Mean NEI VFQ-25 scores improved by more than 7 points from baseline (P<0.01) on 7 of 8 relevant subscales. Eleven eyes did not receive the device because of an aborted procedure. Endothelial cell density was reduced by 20% at 3 months and 25% at 1 year. The decrease in ECD was correlated with postsurgical edema (P<0.0001), and there was no evidence that endothelial cell loss is accelerated by ongoing endothelial trauma after implantation. CONCLUSIONS: This implantable visual prosthesis can improve visual acuity and quality of life in patients with moderate to profound visual impairment caused by bilateral, end-stage AMD.

Activities of Daily Living↗
PubMed2006

Cataract extraction in the collaborative initial glaucoma treatment study: incidence, risk factors, and the effect of cataract progression and extraction on clinical and quality-of-life outcomes.

OBJECTIVES: To study the incidence of and predictors for cataract extraction (CE) in patients with newly diagnosed glaucoma, the impact of CE on visual function, and changes in the time around CE. METHODS: Patients were randomized to medical or surgical treatments for glaucoma at 14 centers and followed up for a median of 7.7 years. Vision-specific quality of life (VS-QOL) data were collected by telephone interview during follow-up of 607 patients randomized to medical or surgical treatments for glaucoma. The occurrence of CE was the signal event. Risk factors were evaluated using survival analyses; changes from before to after CE were evaluated by paired t tests; and trends were estimated by loess regression. RESULTS: During follow-up of 607 patients, CE took place in 99 study eyes. Initial surgery, older age, a more negative spherical equivalent, and a diagnosis of pseudoexfoliative glaucoma conferred a higher risk of CE. Visual field testing before and after CE showed the mean deviation improved but the pattern standard deviation worsened. The VS-QOL improved on most subscales. CONCLUSIONS: Initial surgery places a patient with glaucoma at a higher risk of CE. The impact of CE on visual field indexes is mixed-the mean deviation improved but the pattern standard deviation worsened. Most, but not all, VS-QOL subscales were responsive to worsening of cataract prior to and acute improvement in vision after CE.

Aged↗
PubMed2005

Ordered subset analysis supports a glaucoma locus at GLC1I on chromosome 15 in families with earlier adult age at diagnosis.

Open angle glaucoma (OAG) is a complex disorder with varying etiologies due to multiple genes and environmental effects. This genetic heterogeneity can confound efforts to map loci. Increased homogeneity in a sample can be achieved using either ordered subset analysis (OSA) which groups families, or individual OSA (IOSA), which groups individuals based on disease related covariates. Recently, GLC1I was mapped to 15q11-13 in families with early adult onset of OAG. We tested for linkage to GLC1I in an independent sample of 167 individuals in 25 multiplex OAG families of European descent. We carried out nonparametric linkage analysis on the complete set of 25 families and obtained a maximum LOD score of 1.00 at 9.0 cM. Using mean age at diagnosis (AAD) across the affected individuals within each family to order the families as a proxy for age at onset, we found a maximum OSA LOD score of 2.09 (p=0.021) at 26.1 cM. The mean (+/-s.d.) AAD across the 14 earlier AAD families that contributed to the OSA LOD score was 50.6 years (+/-5.38); the mean AAD for the other 1210 later AAD families that did not contribute to the OSA LOD score (the high-AAD) was 61.7 years (+/-3.50). We also ran IOSA on our families using AAD as our covariate on which to subset affected individuals. The maximum LOD score was 1.01 at 14.3 cM when ordering subjects from early to late AAD. Ordered subset analysis of this sample has provided evidence of linkage close to the previously identified GLC1I glaucoma locus on 15q11-13 in families with middle-aged mean age at diagnosis.

Adolescent↗
PubMed2005

Mutations in TCF8 cause posterior polymorphous corneal dystrophy and ectopic expression of COL4A3 by corneal endothelial cells.

Posterior polymorphous corneal dystrophy (PPCD, also known as PPMD) is a rare disease involving metaplasia and overgrowth of corneal endothelial cells. In patients with PPCD, these cells manifest in an epithelial morphology and gene expression pattern, produce an aberrant basement membrane, and, sometimes, spread over the iris and nearby structures in a way that increases the risk for glaucoma. We previously mapped PPCD to a region (PPCD3) on chromosome 10 containing the gene that encodes the two-handed zinc-finger homeodomain transcription factor TCF8. Here, we report a heterozygous frameshift mutation in TCF8 that segregates with PPCD in the family used to map PPCD3 and four different heterozygous nonsense and frameshift mutations in TCF8 in four other PPCD probands. Family reports of inguinal hernia, hydrocele, and possible bone anomalies in affected individuals suggest that individuals with TCF8 mutations should be examined for nonocular anomalies. We detect transcripts of all three identified PPCD genes (VSX1, COL8A2, and TCF8) in the cornea. We show presence of a complex (core plus secondary) binding site for TCF8 in the promoter of Alport syndrome gene COL4A3, which encodes collagen type IV alpha 3, and we present immunohistochemical evidence of ectopic expression of COL4A3 in corneal endothelium of the proband of the original PPCD3 family. Identification of TCF8 as the PPCD3 gene provides a valuable tool for the study of critical gene regulation events in PPCD pathology and suggests a possible role for TCF8 mutations in altered structure and function of cells lining body cavities other than the anterior chamber of the eye. Thus, this study has identified TCF8 as the gene responsible for approximately half of the cases of PPCD, has implicated TCF8 mutations in developmental abnormalities outside the eye, and has presented the TCF8 regulatory target, COL4A3, as a key, shared molecular component of two different diseases, PPCD and Alport syndrome.

Autoantigens↗
PubMed2005

Toll-like receptor 4 variant D299G is associated with susceptibility to age-related macular degeneration.

Age-related macular degeneration (AMD) is a genetically heterogeneous disease that leads to progressive and irreversible vision loss among the elderly. Inflammation, oxidative damage, cholesterol metabolism and/or impaired function of retinal pigment epithelium (RPE) have been implicated in AMD pathogenesis. We examined toll-like receptor 4 (TLR4) as a candidate gene for AMD susceptibility because: (i) the TLR4 gene is located on chromosome 9q32-33, a region exhibiting evidence of linkage to AMD in three independent reports; (ii) the TLR4-D299G variant is associated with reduced risk of atherosclerosis, a chronic inflammatory disease with subendothelial accumulation; (iii) the TLR4 is not only a key mediator of proinflammatory signaling pathways but also linked to regulation of cholesterol efflux and (iv) the TLR4 participates in phagocytosis of photoreceptor outer segments by the RPE. We examined D299G and T399I variants of TLR4 in a sample of 667 unrelated AMD patients and 439 unrelated controls, all of Caucasian ancestry. Multiple logistic regression demonstrated an increased risk of AMD in carriers of the G allele at TLR4 residue 299 (odds ratio=2.65, P=0.025), but lack of an independent effect by T399I variant. TLR4-D299G showed an additive effect on AMD risk (odds ratio=4.13, P=0.002) with allelic variants of apolipoprotein E (APOE) and ATP-binding cassette transporter-1 (ABCA1), two genes involved in cholesterol efflux. Interestingly, the effect of TLR4, APOE and ABCA1 variants on AMD susceptibility was opposite to that of association with atherosclerosis risk. Our data provide evidence of a link between multiple diverse mechanisms underlying AMD pathogenesis.

Aged↗
PubMed2005

Perioperative complications of trabeculectomy in the collaborative initial glaucoma treatment study (CIGTS).

PURPOSE: To describe the incidence of, and risk factors for, surgical complications reported during and within the first post-operative month after trabeculectomy in the Collaborative Initial Glaucoma Treatment Study (CIGTS). DESIGN: Review of prospectively collected data from a multicenter, randomized clinical trial. METHODS: Complications were tabulated for the 300 CIGTS patients randomized to surgery. Logistic regression analyses were used to identify risk factors for complications. RESULTS: Among the 300 patients randomized to initial surgery, 465 trabeculectomies were performed. Intraoperative complications were reported in 55 eyes (12%). The most frequent reported complications were anterior chamber bleeding during surgery (37 eyes, 8%) and conjunctival buttonhole (five eyes, 1%). Early post-operative complications were reported in 232 eyes (50%). Complications with a frequency over 10% included shallow or flat anterior chamber (62 eyes, 13%), encapsulated bleb (56 eyes, 12%), ptosis (55 eyes, 12%), serous choroidal detachment (52 eyes, 11%), and anterior chamber bleeding or hyphema (48 eyes, 10%). There were three localized suprachoroidal hemorrhages (0.7%) and no cases of endophthalmitis. Older patients were more likely to experience serous choroidal detachment, new anterior or posterior synechiae, and wound leak. Blacks were less likely to experience anterior chamber bleeding, but more likely to experience post-operative ptosis. The number of subjects experiencing bilateral complications was higher than that which would have been predicted by chance alone. CONCLUSIONS: The incidence of transient and self-limiting complications was high in the perioperative period, but we observed few complications with the potential to cause severe sustained vision loss in this group of previously untreated eyes.

Adult↗
PubMed2005

Converting to SITA-standard from full-threshold visual field testing in the follow-up phase of a clinical trial.

PURPOSE: To evaluate the impact of converting from Humphrey 24-2 full-threshold (FT) visual field (VF) testing to SITA-Standard (SS) VF testing during the follow-up phase of a clinical trial. METHODS: VF data were obtained from 243 patients in the Collaborative Initial Glaucoma Treatment Study (CIGTS) who had follow-up visits in 2004. FT and SS VF tests were performed in random order on the same day. RESULTS: The average duration of the SS test (6.3 minutes) was shorter (P < 0.0001, paired t-test) than the FT test (11.8 minutes). The mean deviation did not differ between SS and FT testing. A small difference was found in the pattern SD (PSD) (P = 0.02). The mean CIGTS score from the FT test (4.5) was significantly lower (P < 0.0001) than the mean CIGTS score from the SS test (6.0). Although the two tests yielded identical Glaucoma Hemifield Test (GHT) results in 179 patients (76%), 16 patients had a normal GHT result on FT testing and an SS test result that was outside normal limits. Six patients had the reverse finding. The most significant factor associated with an increased (positive) difference between the CIGTS VF score generated from SS and FT testing was conducting the FT test first (P < 0.0001). CONCLUSIONS: Although SS and FT testing yielded very similar mean deviation results, the CIGTS VF score and GHT differed between SS and FT tests. Changing the approach used to measuring a study's primary VF outcome should be accompanied by a critical evaluation of the change's impact.

Adult↗
PubMed2003

Glaucoma clinical trials and what they mean for our patients.

PURPOSE: To provide a perspective on the several randomized clinical trials in glaucoma, to suggest how their results can be used in clinical practice, and to look to the future of glaucoma therapy. DESIGN: A search and review of the glaucoma clinical trials literature, the glaucoma observational studies literature, and the evidence-based medicine literature. METHODS: Analysis of the significance of glaucoma clinical trials data on patient management along with use of patient data to demonstrate how treatment decisions can be used in the practice setting. RESULTS: Glaucoma clinical trials and observational studies strongly support the need to reduce intraocular pressures (IOP) substantially and to maintain those pressures in patients with advanced glaucoma. Whether this aggressive therapy occurs by medications or by filtering surgery does not seem as important as that the treatment is effective and sustained. However, there is not the same strength of evidence for aggressive treatment or even any treatment for most patients with ocular hypertension and for some cases of early glaucoma. Because about half of the patients with open-angle glaucoma will have IOPs less than 21 mm Hg, these patients need to be detected through careful optic disk and visual field assessment. Once patients are detected and treated appropriately, blindness from open-angle glaucoma is unlikely. CONCLUSIONS: The goal of managing ocular hypertension and glaucoma is not to preserve every ganglion cell, but rather to preserve a patient's visual ability to conduct activities of daily living. Risk factors for damage need to be assessed for individual patients and each patient managed as an individual and not as the "average" patient depicted in the results of clinical trials. In the future, neuroprotective therapy other than IOP reduction will provide another means to control glaucoma damage.

Clinical Trials as Topic↗
PubMed2003

Assessing the need for posterior sclerotomy at the time of filtering surgery in patients with Sturge-Weber syndrome.

PURPOSE: Posterior sclerotomy has been recommended for prevention of intraoperative choroidal hemorrhages and choroidal effusions in patients with Sturge-Weber syndrome (SWS) or Klippel-Trenaunay-Weber (KTW) syndrome undergoing glaucoma filtering surgery. In this study, we evaluated this unproven clinical perception. DESIGN: A retrospective, noncomparative, case series. PARTICIPANTS: Seventeen consecutive patients with SWS or KTW syndrome who underwent glaucoma filtering surgery without prophylactic posterior sclerotomy or other prophylactic measures between January 1973 and March 1997 at a university-based practice. INTERVENTION: Glaucoma filtering surgery without prophylactic posterior sclerotomy. MAIN OUTCOME MEASURES: Incidence of intraoperative and postoperative choroidal effusion, choroidal detachment, or choroidal hemorrhage. RESULTS: No intraoperative choroidal effusion, choroidal detachment, or choroidal hemorrhage occurred in this series. After surgery, 6 patients had a transient choroidal effusion. Surgical drainage was not required in any of them. No suprachoroidal hemorrhages occurred after surgery. CONCLUSIONS: We did not encounter significant intraoperative suprachoroidal hemorrhage, choroidal effusions, or a combination requiring therapeutic intervention in our series. This finding leads us to question the necessity for prophylactic posterior sclerotomy to prevent the occurrence of these complications in patients with SWS and KTW syndrome undergoing glaucoma filtering surgery.

Choroid Diseases↗
PubMed2003

Septuagenarian's phenotype leads to ascertainment of familial MYOC gene mutation.

PURPOSE: To report a family with a myocilin (MYOC) gene mutation ascertained on the basis of the phenotype of the 71-year-old proband with juvenile-onset primary open-angle glaucoma (JOAG). PATIENTS AND METHODS: A thorough patient history of the proband and review of medical records revealed that a filtering procedure performed 50 years before had controlled the intraocular pressure (IOP) and prevented optic disc damage and visual field loss until the bleb failed after cataract surgery. Patient characteristics and history led to suspicion of a mutation in the MYOC gene. Mutation screening and clinical evaluation of the proband and family members were undertaken. RESULTS: A Val426Phe mutation was found in the JOAG proband and in 3 other blood relatives with glaucoma. The mutation was not present in unaffected relatives. CONCLUSIONS: A functioning filtering procedure performed 50 years before the current study was all that was needed to prevent glaucomatous damage and control IOP in the proband. Once the bleb failed, increased IOP led to damage in a relatively brief period of time. Although not every JOAG patient has the MYOC mutation, there is a somewhat typical MYOC phenotype that may predict an increased chance of harboring a MYOC mutation. Use of such phenotype information in evaluating whether to screen older patients can lead to identification of families at risk for open-angle glaucoma.

Adolescent↗
PubMed2003

The collaborative initial glaucoma treatment study: baseline visual field and test-retest variability.

PURPOSE: To compare the baseline Collaborative Initial Glaucoma Treatment Study (CIGTS) visual field (VF) score and mean deviation (MD), investigate test-retest variability, and identify variables associated with VF loss and VF measurement variability. METHODS: Baseline data from a randomized clinical trial of 607 patients with newly diagnosed open-angle glaucoma were collected at 14 clinical centers. The CIGTS VF score and MD were obtained from 24-2 VF tests (Zeiss-Humphrey Systems, Dublin, CA) at two visits approximately 2 weeks apart. RESULTS: Although most baseline CIGTS VF scores showed limited field loss, 15% (91/607) of patients showed a substantial deficit (VF score >10 on a 0-20 scale). A small but significant learning effect was seen over the two baseline measures for CIGTS VF score and MD. CIGTS VF score and MD correlate highly (r = -0.93); both have high test-retest correlation (0.83 and 0.91, respectively). Variables associated with greater baseline VF loss for both CIGTS VF score and MD include (probabilities for VF only): male sex (P = 0.018), black race (P <or= 0.0001), lower visual acuity (P <or= 0.0001), higher intraocular pressure if more than 30 mm Hg (P = 0.0034), poor field reliability score (P <or= 0.0001), cardiovascular disease (P = 0.015), reduced patient-reported alertness (P = 0.023), and CIGTS clinical center (P <or= 0.0001). Predictors of increased CIGTS VF score variability include a midrange VF score (P <or= 0.0001), first-tested eye (P = 0.0027), reduced patient-reported alertness (P = 0.0177), increasing age (P = 0.0040), current smoker (P = 0.0014), and CIGTS clinical center (P = 0.0215). CONCLUSIONS: The CIGTS VF score provides a measure of VF strikingly similar to the MD. Variables associated with VF loss and VF variability may help identify patients who need greater clinical scrutiny.

Adult↗