Elimination of the color discrimination impairment along the blue-yellow axis in patients with hypothyroidism after treatment with levothyroxine as assessed by the Farnsworth-Munsell 100 hue test.

Our previous study has shown that individuals with untreated hypothyroidism display significantly higher partial error scores (P E S) along the blue-yellow axis compared to the red-green axis than normal individuals using the Farnsworth-Munsell 100 hue test [J. Opt. Soc. Am. A37, A18 (2020)JOAOD60740-323210.1364/JOSAA.382390]. We wished to determine how color discrimination may change when hypothyroidism has been treated to the point of euthyroidism. Color discrimination was reassessed for 17 female individuals who had undergone treatment for hypothyroidism, and the results were compared with 22 female individuals without thyroid dysfunction. No statistically significant difference was found in the total error score (T E S) for the first and second measurements for both groups (p>0.45). The P E S for the hypothyroid group improved significantly in the previously impaired color regions after the treatment. Color discrimination defects found in untreated hypothyroidism can be negated with treatment of the condition over an appropriate time period.

Complete recovery of visual acuity as the main goal of treatment in patients with dysthyroid optic neuropathy.

INTRODUCTION: To evaluate the effectiveness of methylprednisolone (MP) and surgical treatment in achieving complete reversal of dysthyroid optic neuropathy (DON) and predictive factors of this therapy. MATERIAL AND METHODS: The group consisted of 10 patients (18 eyes) with DON. The diagnosis of DON was based on at least two criteria from the following: (i) deterioration of visual acuity (VA< 1.0), (ii) loss of colour vision, (iii) optic disc swelling, and/or (iv) signs of DON in magnetic resonance imaging (presence of apical crowding and/or optic nerve stretching). A complete recovery of DON was defined as the normalisation of VA (VA = 1.0), normal colour vision, and reversal of optic disc swelling. A significant improvement was defined as improvement of VA of at least 0.2. The consecutive steps of treatment of DON consisted of: (i) first-line treatment - intravenous MP pulse therapy (3 × 1 g); (ii) second-line treatment - endoscopic intranasal orbital decompression of medial wall; (iii) additional treatment - additional MP therapy and/or surgical decompression. RESULTS: A significant improvement in VA could be achieved in the majority of patients; a complete recovery was noted in 22.2%, 33.3%, and 66.7% of eyes after first-line, second-line, and additional treatment, respectively. Positive predictive factors were: younger age (p = 0.049), shorter duration of DON (p = 0.035), and a higher Graves' orbitopathy clinical activity score (p = 0.035). CONCLUSIONS: By using combination therapy (intravenous MP pulse therapy and surgical decompression), a complete recovery can be achieved in the majority of patients with DON.

Intravitreal Ciliary Neurotrophic Factor Transiently Improves Cone-Mediated Function in a CNGB3-/- Mouse Model of Achromatopsia.

PURPOSE: Ciliary neurotrophic factor (CNTF) was recently shown to augment cone function in CNGB3 mutant achromat dogs. However, testing CNTF-releasing implant in human CNGB3 achromats failed to show benefit. We evaluated the effects of CNTF protein on the retinal function in an additional achromatopsia model, the CNGB3-/- mouse. METHODS: Fifty-nine CNGB3-/- mice (postnatal day [PD] ± SD = 30 ± 7) received a unilateral intravitreal injection of 1 or 2 µg CNTF protein, and 15 wild-type (WT) mice (PD = 34 ± 3) received 1 µg CNTF. Retinal function was evaluated by flash ERG and photopic flicker ERG (fERG) at 7 and 14 days after treatment. RESULTS: Seven days post CNTF, the photopic b-wave Vmax was significantly increased in CNGB3-/- mice (P < 0.01), whereas it was reduced in WT mice (P < 0.05). Ciliary neurotrophic factor significantly increased the amplitude of photopic fERG and the photopic oscillatory potentials (OPs) in CNGB3-/- mice. Ciliary neurotrophic factor did not alter the scotopic a-wave in either CNGB3-/- or WT mice, but it increased the scotopic b-wave k (P < 0.01) in CNGB3-/- mice, indicating diminished scotopic sensitivity, and reduced the scotopic b-wave Vmax in WT mice (P < 0.05). No difference was found in ERG parameters between 1 or 2 µg CNTF. Fourteen days after CNTF injection the ERG changes in CNGB3-/- mice were lost. CONCLUSIONS: Intravitreal bolus CNTF protein caused a small and transient improvement of cone-mediated function in CNGB3-/- mice, whereas it reduced rod-mediated function. The increase in photopic OPs and the lack of changes in scotopic a-wave suggest a CNTF effect on the inner retina.

CNGB3-achromatopsia clinical trial with CNTF: diminished rod pathway responses with no evidence of improvement in cone function.

PURPOSE: Ciliary neurotrophic factor (CNTF) protects rod photoreceptors from retinal degenerative disease in multiple nonhuman models. Thus far, CNTF has failed to demonstrate rod protection in trials for human retinitis pigmentosa. Recently, CNTF was found to improve cone photoreceptor function in a canine CNGB3 achromatopsia model. This study explores whether this finding translates to humans with CNGB3 achromatopsia. METHODS: A five-subject, open-label Phase I/II study was initiated by implanting intraocular microcapsules releasing CNTF (nominally 20 ng/d) into one eye each of CNGB3 achromat participants. Fellow eyes served as untreated controls. Subjects were followed for 1 year. RESULTS: Pupil constriction in treated eyes gave evidence of intraocular CNTF release. Additionally, scotopic ERG responses were reduced, and dark-adapted psychophysical absolute thresholds were increased, attributable to diminished rod or rod pathway activity. Optical coherence tomography revealed that the cone-rich fovea underwent structural changes as the foveal hyporeflective zone (HRZ) became diminished in CNTF-treated eyes. No objectively measurable enhancement of cone function was found by assessments of visual acuity, mesopic increment sensitivity threshold, or the photopic ERG. Careful measurements of color hue discrimination showed no change. Nonetheless, subjects reported beneficial changes of visual function in the treated eyes, including reduced light sensitivity and aversion to bright light, which may trace to decreased effective ambient light from the pupillary constriction; further they noted slowed adaptation to darkness, consistent with CNTF action on rod photoreceptors. CONCLUSIONS: Ciliary neurotrophic factor did not measurably enhance cone function, which reveals a species difference between human and canine CNGB3 cones in response to CNTF. (ClinicalTrials.gov number, NCT01648452.).

Suppressing thyroid hormone signaling preserves cone photoreceptors in mouse models of retinal degeneration.

Cone phototransduction and survival of cones in the human macula is essential for color vision and for visual acuity. Progressive cone degeneration in age-related macular degeneration, Stargardt disease, and recessive cone dystrophies is a major cause of blindness. Thyroid hormone (TH) signaling, which regulates cell proliferation, differentiation, and apoptosis, plays a central role in cone opsin expression and patterning in the retina. Here, we investigated whether TH signaling affects cone viability in inherited retinal degeneration mouse models. Retinol isomerase RPE65-deficient mice [a model of Leber congenital amaurosis (LCA) with rapid cone loss] and cone photoreceptor function loss type 1 mice (severe recessive achromatopsia) were used to determine whether suppressing TH signaling with antithyroid treatment reduces cone death. Further, cone cyclic nucleotide-gated channel B subunit-deficient mice (moderate achromatopsia) and guanylate cyclase 2e-deficient mice (LCA with slower cone loss) were used to determine whether triiodothyronine (T3) treatment (stimulating TH signaling) causes deterioration of cones. We found that cone density in retinol isomerase RPE65-deficient and cone photoreceptor function loss type 1 mice increased about sixfold following antithyroid treatment. Cone density in cone cyclic nucleotide-gated channel B subunit-deficient and guanylate cyclase 2e-deficient mice decreased about 40% following T3 treatment. The effect of TH signaling on cone viability appears to be independent of its regulation on cone opsin expression. This work demonstrates that suppressing TH signaling in retina dystrophy mouse models is protective of cones, providing insights into cone preservation and therapeutic interventions.

Chromatic visual phenomenon caused by a subluxed intraocular lens.

A 74-year-old man developed an unusual chromatic aberration as a complication of cataract extraction surgery with posterior chamber intraocular lens implantation. The patient could see the location and color of one of the haptics of the dislocated lens. His symptoms resolved with miotic therapy.

Whole blood cyanide levels in patients with tobacco amblyopia.

Three patients presented with painless bilateral visual failure due to tobacco amblyopia. The whole blood cyanide levels were raised above those predicted from their high tobacco consumption, approaching lethal levels reported from acute inhalation of cyanide. Each patient had an excessive alcohol intake with biochemical evidence of hepatic dysfunction, the elevated whole blood cyanide levels being attributed to the associated impairment of cyanide detoxification. In each case the improvement in visual acuities following abstinence and hydroxycobalamin therapy was accompanied by a reduction in the whole blood cyanide level to within the normal range. Serial measurements of whole blood cyanide, serum alcohol, and the detection of urinary nicotine provided valuable indices of the patient's subsequent compliance and clinical progress.