CRB1 gene mutations are associated with keratoconus in patients with leber congenital amaurosis.

PURPOSE: To present an association of mutations in the CRB1 gene with keratoconus in patients with Leber congenital amaurosis (LCA). METHODS: Sixteen patients with genotyped LCA (having the CRB1, CRX, RetGC, RPE65, and AIPL1 mutations) were recruited from one ophthalmology practice and examined for the presence of keratoconus. Corneal topography, visual acuity, and slit lamp biomicroscopic examination were performed in all cases. RESULTS: The mean age of the patients was 34.5 years (range, 13-74). Visual acuities ranged from 20/40 to light perception. Corneal topography was successfully collected in 15 of the cases. Five of the 16 cases had slit lamp and/or topographic features consistent with keratoconus. One patient had a clinical picture that was keratoglobus-like. Of these six cases, four had a CRB1 mutation and two had a CRX mutation. Of the three subjects with the CRX mutation, one had keratoconus, one had the keratoglobus-like presentation, and one was normal. Our cohort represents 14 separate, unrelated families. Only one family comprised multiple members with LCA. These were three affected brothers, one with keratoconus, all with CRB1 mutations. CONCLUSIONS: Although the results cannot exclude other gene mutations, they suggest that LCA patients with a CRB1 mutation may have a particular susceptibility to keratoconus.

Spontaneous improvement of rod system function in a patient with melanoma-associated retinopathy.

PURPOSE: To report spontaneous improvement of rod visual function in a patient with melanoma-associated retinopathy (MAR). METHODS: Electroretinography (ERG), and dark-adapted psychophysical thresholds were performed on a male patient with the MAR syndrome, during four visits over a period of almost 7 years. RESULTS: There was a spontaneous, subjective improvement in night vision and a decrease in the severity of photopsias of the patient's left eye between the initial and most recent visits. Both the dark-adapted rod-isolated and maximal-flash b-wave ERG amplitude also improved his initial visit to the most recent visit. By comparison, the light-adapted brief-flash and flicker ERG amplitudes were initially within the range of normal in the left eye but showed a subsequent reduction in amplitude. The ERG response of the right eye was only measured at the most recent visit, but gave a dark-adapted response that was similar to that of the left eye on the initial visit, and a light-adapted response that was similar to that of the left eye on the most recent visit. Rod sensitivity was substantially better in the left eye than in the right eye by psychophysical testing, although the right eye did show a noticeable level of improvement in rod thresholds between the initial and most recent visits. CONCLUSIONS: These findings document the potential for spontaneous improvement in electrophysiological and psychophysical rod function, as well as in subjective symptoms, in patients with the MAR syndrome.

Intersession repeatability of humphrey perimetry measurements in patients with retinitis pigmentosa.

PURPOSE: To determine the relationship between intersession test repeatability in static perimetry and the degree of local sensitivity reduction in patients with retinitis pigmentosa (RP). METHODS: Visual field data were obtained from 27 patients with RP using FASTPAC 30-2 of the Humphrey Field Analyzer and stimulus sizes III and V. Each test was repeated at two subsequent visits after an initial practice session. An intersession sensitivity difference was defined for each patient at each measured point in the visual field by subtracting the sensitivity value obtained during session 2 from the value obtained during session 3 at the corresponding test location. In addition, the mean sensitivity value for sessions 2 and 3 was determined at each location for each patient. RESULTS: Bland-Altman plots of intersession sensitivity differences as a function of mean sensitivities showed that test-retest variability was greatest at test regions with sensitivities of approximately 10 dB, with lower variability at locations with higher or lower sensitivity. The pattern of findings was similar for sizes III and V stimuli. The mean intersession sensitivity difference was +0.26 dB for stimulus size III and +0.45 dB for stimulus size V, representing a small improvement in sensitivity from session 2 to session 3. CONCLUSIONS: Intersession repeatability of visual field measurements in patients with RP is nonmonotonically related to the magnitude of the sensitivity loss. Therefore, apparent changes in visual field sensitivity as a result of time or treatment should be evaluated in light of the degree of the expected variability at particular sensitivity levels.

Retinal dysfunction in carriers of bardet-biedl syndrome.

PURPOSE: To determine whether retinal dysfunction in obligate carriers of the Bardet-Biedl syndrome (BBS) could be observed in local electroretinographic responses obtained with the multifocal electroretinogram (mfERG). METHODS: Six obligate carriers of the BBS were examined for the study. Examination of each carrier included an ocular examination and mfERG testing of one eye. For the mfERG, we used a 103-scaled hexagonal stimulus array that subtended a retinal area of approximately 40 degrees in diameter. The amplitudes and implicit times in each location for the mfERG were compared with the corresponding values determined for a group of 34 normally sighted, age-similar control subjects. RESULTS: Mapping of 103 local electroretinographic response amplitudes within a central 40 degrees area with the mfERG showed regions of reduced mfERG amplitudes in three of six carriers. Implicit time measurements in the 6 carriers were all normal except for those locations associated with abnormal amplitude reductions in 3 of the carriers. When present, retinal dysfunction was evident in the presence of a normal-appearing fundus. CONCLUSIONS: Multifocal ERG testing can demonstrate areas of retinal dysfunction in carriers of the BBS. This test may therefore be useful for identifying some heterozygous carriers of this disease.

Multifocal ERG findings in carriers of X-linked retinoschisis.

PURPOSE: To determine whether retinal dysfunction in obligate carriers of X-linked retinoschisis (XLRS) could be observed in local electroretinographic responses obtained with the multifocal electroretinogram (mfERG). METHODS: Nine obligate carriers of XLRS (mean age, 46.2 years) were examined for the study. Examination of each carrier included an ocular examination and mfERG testing. For the mfERG, we used a 103-scaled hexagonal stimulus array that subtended a retinal area of approximately 40 degrees in diameter. The amplitudes and implicit times in each location for the mfERG were compared with the corresponding values determined for a group of 34 normally-sighted, age-similar control subjects. RESULTS: Mapping of 103 local electroretinographic response amplitudes and implicit times within a central 40 degrees area with the mfERG showed regions of reduced mfERG amplitudes and delayed implicit times in two of nine carriers. CONCLUSIONS: The mfERG demonstrated areas of retinal dysfunction in two carriers of XLRS. When present, retinal dysfunction was evident in the presence of a normal-appearing fundus. Multifocal ERG testing can be useful for identifying some carriers of XLRS.

Hormone replacement therapy in menopausal women: Past problems and future possibilities.

Oral administration of conjugated equine estrogens (CEE) with and without the synthetic progestin medroxyprogesterone acetate (MPA) in postmenopausal women is associated with side-effects that include increased risk of stroke and breast cancer. The current evidence that transdermal administration of estradiol may provide a safer alternative to orally administered CEE is reviewed. Transdermally administered estradiol has been shown to be an efficacious treatment for hot flushes possibly without the increase in blood clotting that is associated with administration of oral CEE. Further, natural progesterone may have a more beneficial spectrum of physiological effects than synthetic progestins. The substantial differences between CEE compared with estradiol and estriol, as well as the differences between synthetic MPA and natural progesterone, are detailed. Estriol is an increasingly popular alternative hormone therapy used for menopausal symptoms. There is evidence that estriol, by binding preferentially to estrogen receptor-beta, may inhibit some of the unwanted effects of estradiol. New clinical trials are needed to evaluate the safety and efficacy of topically or transdermally administered combinations of estradiol, estriol and progesterone. Future studies should focus on relatively young women who begin estrogen supplement use near the start of menopause.

Is bio-identical hormone replacement therapy safer than traditional hormone replacement therapy?: a critical appraisal of cardiovascular risks in menopausal women.

Recent clinical trials have demonstrated an increase in the risk of cardiovascular disease (CVD) in women using oral hormone replacement therapy (HRT). Bio-identical HRT (BHRT) is widely used by alternative healthcare practitioners for the treatment of symptoms of menopause, with the prevailing assumption that BHRT provides the benefits of HRT while attenuating the risks. However, considering the serious risks of HRT, the use of any form of HRT, including BHRT, without sufficient scientific evaluation may create considerable risk.The main hormone found in BHRT is estriol. Estriol is used alone or in combination with estradiol and estrone. The total daily oral dose of BHRT used is, on average, ten times higher than that used in HRT, and both oral and topical forms are used for bio-identical hormone administration. The clinical trials that have examined cardiovascular outcomes associated with estriol therapy are limited, and there is evidence to demonstrate variable effects on markers associated with cardiovascular risk.Based on the current evidence, the same cardiovascular risks that have recently been found to be associated with oral HRT may also be associated with the administration of oral estriol in BHRT. The use of oral bio-identical hormones cannot be promoted until further evidence is available to demonstrate its safety.

Comparison of visual acuity loss in patients with different stages of Stargardt's disease.

PURPOSE: To investigate a previously reported observation that the presence of diffuse, as compared with localized, fundus flecks is an indicator of a more severe course for visual acuity (VA) loss beyond 20/200 in patients with Stargardt's disease. DESIGN: Retrospective clinic-based cross-sectional study. PARTICIPANTS: Four hundred five patients with Stargardt's disease. METHODS: Visual acuity in 405 patients with Stargardt's disease was analyzed at their initial and most recent visits. The stage of Stargardt's disease and appearance of the macula were recorded. The diagnosis and stage of Stargardt's disease were based on the extent and appearance of fundus flecks. MAIN OUTCOME MEASURES: Best-corrected VA, stage of Stargardt's disease, and appearance of the macula at the initial and most recent visits were used in the cross-sectional analysis. RESULTS: At their initial visit, 199 patients were identified as having stage 1 Stargardt's disease, of whom 97.5% maintained 20/200 or better VA in at least one eye. One hundred eighty-five were identified as having stage 2 or stage 2-3 Stargardt's disease combined, of whom 83.2% maintained 20/200 VA or better. Patients with stage 1 were more likely to maintain 20/200 or better VA in at least one eye when compared with patients with stage 2/stage 2-3 Stargardt's disease (chi2(1) = 21.25, P<0.001). Ninety-nine percent of stage 1 patients and 94.1% of stage 2/stage 2-3 patients maintained 20/400 or better VA in at least one eye (chi2(1) = 5.72, P = 0.017). CONCLUSIONS: Patients with stage 1 Stargardt's disease exhibiting fundus flecks limited to the posterior pole are more likely to maintain a level of VA at 20/200 or better when compared with patients with stage 2/stage 2-3 disease who have diffuse fundus flecks. Nevertheless, over 80% of the patients with stage 2/stage 2-3 Stargardt's disease still maintained VA of 20/200 or better. Only 5.9% of patients with stage 2/stage 2-3 had VA levels worse than 20/400. In our cohort of patients with Stargardt's disease and diffuse fundus flecks, the majority of patients did not lose VA to a greater extent than those with localized flecks.

Evidence for a learning effect in short-wavelength automated perimetry.

PURPOSE: To document the magnitude of any learning effect for short-wavelength automated perimetry (SWAP) in patients with either ocular hypertension (OHT) or open-angle glaucoma (OAG) who are experienced in standard automated perimetry (SAP). DESIGN: Experimental study. PARTICIPANTS: Thirty-five patients (22 with OHT and 13 with OAG) who had previously undergone at least 3 threshold SAP visual field examinations with the Humphrey Field Analyzer (HFA; Carl Zeiss Meditech Inc., Dublin, CA), and 9 patients with OHT who had not previously undertaken any form of perimetry. METHODS: Each patient attended for SWAP on 5 occasions, each separated by 1 week. At each visit, both eyes were examined using Program 24-2 of the HFA; the right eye was always examined before the left eye. MAIN OUTCOME MEASURES: (1) Change over the 5 examinations, in each eye, of the visual field indices Mean Deviation (MD), Short-term Fluctuation (SF), Pattern Standard Deviation (PSD), and Corrected Pattern Standard Deviation. (2) Change in each eye between Visits 1 and 5 in proportionate Mean Sensitivity (pMS) for the central annulus of stimulus locations compared with that for the peripheral annulus thereby determining the influence of stimulus eccentricity on any alteration in sensitivity. (3) Change between Visits 1 and 5 in the number and magnitude of the Pattern Deviation (PD) probability levels associated with any alteration in sensitivity. RESULTS: The MD, SF, and PSD each improved over the 5 examinations (each at P<0.001). The improvement in pMS between Visits 1 and 5 was greater for the peripheral annulus than for the central annulus by approximately twofold for the patients with OAG. Considerable variation was present between patients, within and between groups, in the number of locations exhibiting an improving sensitivity between Visits 1 and 5 by 1 or more PD probability levels. CONCLUSIONS: Care should be taken to ensure that, during the initial examinations, apparent field loss with SWAP in patients exhibiting a normal field by SAP is not the result of inexperience in SWAP. Apparently deeper or wider field loss in the initial examinations with SWAP compared with that exhibited by SAP in OAG also may arise from inexperience in SWAP.

The potential of 5-hydryoxytryptophan for hot flash reduction: a hypothesis.

Hormone replacement therapy (HRT) is contraindicated in women with a history of breast cancer or a high risk of breast cancer development. Recent results from large clinical trials, such as the Women's Health Initiative, have demonstrated increased risks of thromboembolic events and a moderate increased risk of breast cancer in women using conjugated estrogens and progestogens. There is a need for viable non-hormonal alternative treatments to HRT, such as nutritional and botanical therapies, in this population of women, who tend to experience more significant vasomotor symptoms. Safe and effective therapies that do not stimulate breast cell proliferation could prove extremely useful for the management of such symptoms for women in both low- and high-risk breast cancer populations. As a non-hormonal treatment, anti-depressants, such as selective serotonin reuptake inhibitors (SSRIs), have been shown to improve hot flash symptoms in women. The proposed mechanism is related to an increase in serotonin allowing for an increase in the set point of the brain's thermoregulator. In small clinical studies, the administration of tryptophan and 5-hydroxytryptophan (5HTP), the precursors of serotonin, have been shown to reduce depressive symptoms, possibly by enhancing the synthesis of serotonin. Thus, increased serotonin levels may have the ability to decrease hot flashes in a mechanism similar to that of SSRIs without the risks of breast cell stimulation. This would be particularly desirable for menopausal women with breast cancer or with risks of breast cancer. This article discusses the background information on hot flashes, SSRIs, tryptophan, and 5HTP, and possible clinical application of 5HTP for menopausal women with breast cancer risk.

A pilot study to examine a combination botanical for the treatment of menopausal symptoms.

OBJECTIVE: Hormone replacement therapy has become a controversial treatment for symptoms of menopause, leading many women and their physicians to search for safer, effective alternatives. Certain botanicals are known to contain phytoestrogenic activity, which may be helpful in alleviating menopausal symptoms. We report the results of a study using a combination botanical supplement to treat menopausal symptoms. DESIGN: Prospective pilot study. SETTING/LOCATION: Family practice medical center, Phoenix metropolitan area. SUBJECTS: Eight (8) women with moderate vasomotor and somatic symptoms of menopause. INTERVENTION: Combination botanicals daily for 3 months. OUTCOME MEASURES: Modified Kupperman Index (KI), daily hot flashes severity, and overall quality of life (QoL) using the SF-36 index, which were collected at enrollment, during treatment, and at the end of treatment. RESULTS: Mean KI total symptoms decreased from 30.3 +/- 7.5 to 22.9 +/- 8.4 (95% CI, 25-34), p = 0.0028. Daily hot flashes decreased from 68.1 +/- 14.3 to 39.6 +/- 9.7 (95% CI, 38-46), p = 0.0003, and the overall QoL also improved at the end of treatment. CONCLUSIONS: This pilot study demonstrates the potential benefit of a combination botanical for improving moderate menopausal symptoms in women. The efficacy and role of combination botanicals for long-term use to reduce menopausal symptoms requires further exploration.

Treatment of seasonal allergic rhinitis using homeopathic preparation of common allergens in the southwest region of the US: a randomized, controlled clinical trial.

BACKGROUND: Studies using homeopathy have reported beneficial effects from treating allergy-related conditions. OBJECTIVE: To investigate the effects of a homeopathic drug prepared from common allergens (tree, grass, weed species) specific to the Southwest region of the US. METHODS: A 4-week, double-blind clinical trial comparing homeopathic preparations with placebo was conducted in the Phoenix metropolitan area during the regional allergy season from February to May. Participants included 40 men and women, 26-63 years of age, diagnosed with moderate to severe seasonal allergic rhinitis symptoms. Study outcomes included allergy-specific symptoms using the rhinoconjunctivitis quality-of-life questionnaire (RQLQ), functional quality of life using the Medical Outcomes Study Short Form-36 (MOS SF-36), and the work productivity and activity impairment (WPAI) questionnaire. RESULTS: Scales from the RQLQ, MOS SF-36, and WPAI questionnaire showed significant positive changes from baseline to 4 weeks in the homeopathic group compared with the placebo group (p < 0.05). Subjects reported no adverse effects during the intervention period. CONCLUSIONS: These preliminary findings indicate potential benefits of the homeopathic intervention in reducing symptoms and improving quality of life in patients with seasonal allergic rhinitis in the Southwestern US.

Immunological activity of larch arabinogalactan and Echinacea: a preliminary, randomized, double-blind, placebo-controlled trial.

UNLABELLED: The immunomodulating effects of two Echinacea species, E. purpurea and E. angustifolia and larch arabinogalactan extracted from Larix occidentalis were examined in a randomized, double-blind, placebo-controlled, prospective four-week clinical trial at a naturopathic medical school research center. SUBJECTS/MATERIALS: Forty-eight healthy female volunteers (22-51 y) were randomly assigned to one of six groups: standardized extract of E. purpurea (EP); ultra-refined E. purpurea/E. angustifolia (urEPA); E. purpurea/E. angustifolia (EPA); E. purpurea/E. angustifolia plus larch arabinogalactan (EPALA); larch arabinogalactan (LA); or placebo. METHODS: Immunological tests with enumerative measurements, stool cultures for Lactobacillus acidophilus and yeast, and health-related quality of life (HRQoL) using the Medical Outcomes Study derived SF-36 self-administered questionnaire were assessed at baseline and at four weeks. RESULTS: Complement properdin increased by 21 percent in the EPA group (p<0.05) and by 18 percent in the EPALA group (p<0.05), compared to the placebo group (p>0.05). SF-36 showed improvements in overall physical health, vitality, and emotional health in the same two groups (EPA and EPALA). DISCUSSION: Volunteers in the EPA and EPALA groups had increased production of complement properdin after four weeks of intervention. The increased complement properdin may be an indication of one aspect of immune system stimulation in patients treated with either E. purpurea/E. angustifolia or E. purpurea/E. angustifolia plus larch arabinogalactan.