OBJECTIVE: To evaluate the effect of topical carbonic anhydrase inhibitor (brinzolamide) versus placebo on visual function and waveforms in infantile nystagmus syndrome (INS).
METHODS: Prospective, placebo-controlled, double-blind, cross-over study.
METHODS: Setting- A tertiary eye care center. Patients- Cases of idiopathic INS with and without abnormal head posture aged ≥10 years who had not received previous treatment for nystagmus. Intervention- Patients were randomized into two groups. Group 1 was given placebo for 3 months, and after a washout period of 7 days started on topical brinzolamide for the next 3 months. In group 2, the order was reversed. The drops were administered topically three times (every 8 hours) in both eyes. Outcome measure- Binocular best corrected visual acuity (BCVA) using the ETDRS chart, eXpanded nystagmus acuity function (NAFX) score and INS waveforms obtained from eye movement recordings, intraocular pressure (IOP) by Goldmann applanation tonometer, near stereopsis by TNO stereo test, and change in abnormal head posture before and after intervention in the null position.
RESULTS: A total of 29 cases completed the study (23 with abnormal head posture; 6 without abnormal head posture).
A significant improvement was noted in INS waveform characteristics, mean NAFX score (P < 0.001), and mean binocular visual acuity (P < 0.001) with topical brinzolamide in comparison to baseline as well as placebo. No significant change in head position and stereopsis was noted. No side effects were reported with 3 months of brinzolamide therapy.
CONCLUSIONS: While brinzolamide shows improvement in visual acuity and NAFX score in idiopathic INS, its clinical significance needs further evidence.

CONCLUSIONS: This multicenter study assessed clinical and psychological aspects of infantile nystagmus syndrome (INS) focusing on its management and nonsurgical treatment.
OBJECTIVE: This study aimed to assess clinical features, management, relationship life, and psychological impact in a group of patients with nystagmus onset in pediatric age.
METHODS: This observational study included patients diagnosed with INS referred to two Italian centers from January 1, 2017, to December 31, 2020. Ophthalmologic and orthoptic features and impact of visual function on quality of life, according to nystagmus-specific nystagmus quality of life questionnaire, were analyzed within the overall sample and in any of INS subgroups.
RESULTS: Forty-three patients were included; 65.1% of them had idiopathic INS (IINS), and 34.9% had INS associated with ocular diseases (INSOD). The median age was 15.4 years (interquartile range [IQR], 10.4 to 17.3 years), significantly different between groups (median, 15.8 years among those with IINS vs. 12.3 years among those with INSOD; p<0.001). In the INSOD subgroup, strabismus was significantly more prevalent (93.3 vs. 57.1%; p=0.017). Binocular distance best-corrected visual acuity in primary position was significantly higher in the IINS subsample (p<0.001). Such behavior was further confirmed at anomalous head position evaluation (p<0.001). At near best-corrected visual acuity assessment, differences between groups were more remarkable in primary position (p<0.001) than in anomalous head position. Contrast sensitivity showed significantly higher values in the IINS subgroup (p<0.001). The nystagmus quality of life questionnaire disclosed a significantly lower score in IINS as compared with INSOD (median total score, 90.5 [IQR, 84 to 97] vs. 94 [IQR, 83.0 to 96.5]; p<0.001).
CONCLUSIONS: The IINS group showed significantly better ophthalmologic and orthoptic outcomes than the INSOD group. The psychological and quality-of-life impact was instead significantly greater in the IINS group. To the best of our knowledge, this is the first multicenter study investigating the clinical features of IIN and comparing the two main subgroups, IINS and INSOD.

BACKGROUND: Establishing eye contact between infants and parents is important for early parent-child bonding and lack of eye contact may be a sign of severe underlying disease. The aim of the study was to evaluate the causes of poor or lacking eye contact in infants.
METHODS: Cross-sectional study reviewing all referrals of infants ≤1 year of age from January 1rst, 2016 to December 31rst, 2018. Medical information was retrieved from patient files covering pregnancy, birth, diagnostic work-up and ocular parameters such as refraction, visual acuity and structural findings.
RESULTS: We identified 99 infants with poor or lacking eye contact. The relative frequency of causes was neurologic disease 36.4% (36/99), delayed visual maturation 24.2% (24/99), ocular disease 21.2% (21/99) and idiopathic infantile nystagmus 4.0% (4/99). Fourteen infants had a visual function within age-related norms at first examination despite poor eye contact at the time of referral. Of the infants with available data, 18/27 (33.3%) with neurologic cause, 15/23 (65.2%) with delayed visual maturation and 9/21 (42.9%) with ocular cause had visual acuity within the age-related norm at latest follow-up (0-41 months). In 23 infants, a genetic cause was found.
CONCLUSIONS: Poor eye contact in infants may be a sign of severe underlying disease, such as neurological or ocular disease. Close collaboration between pediatric ophthalmologists and neuro-pediatricians are warranted in the management of these infants.

UNASSIGNED: Biofeedback training (BT) was adapted to idiopathic infantile nystagmus syndrome (IINS) cases to enhance visual functions and quality of life (QoL).
UNASSIGNED: 10 patients (age 9 ± 3.2 years) treated with the audio-visual BT module of the MAIA microperimeter (Centervue, Padova, Italy) were assessed in two baseline visits and 1week post-BT (BT 80 min in total). The outcomes were distance and near binocular best corrected visual acuity (BBCVA), fixation stability, reading speed, contrast sensitivity, stereopsis and Children\'s Visual Function Questionnaire. One-way repeated measured ANOVA and paired t-tests were used.
UNASSIGNED: Distance BBCVA improved from 0.46 ± 0.21 and 0.43 ± 0.18 pre-BT to 0.33 ± 0.2 logMAR post-BT (F (2,27) = 13.75, p = 0.0002). Post-BT was better than baseline (p = 0.0001) and pre-BT (p = 0.001). Near BBCVA improved from 0.23 ± 0.09 and 0.21 ± 0.14 pre-BT to 0.04 ± 0.08 post-BT (F (2,27) = 22.12, p = 0.000014), post-BT was better than baseline (p = 0.0001) and pre-BT (p = 0.0006). Stereopsis improved from 283 ± 338″ to 39 ± 32.2″ (p = 0.04), contrast sensitivity from 0.26 ± 0.17 to 0.08 ± 0.12 log units (p = 0.01), and reading speed improved from 74.7 ± 51.2 wpm to 104.7 ± 53.6 wpm (p = 0.0006). Fixation stability improved from 33.6 ± 28.1 to 14.3 ± 10.1 sq. QoL increased from 23.8 ± 2.2 to 26.3 ± 2.3 units (p = 0.001).
UNASSIGNED: BT benefited all visual functions and QoL in this pilot study, heralding a new possibility for Low Vision Rehabilitation in IINS.

To evaluate structural grading and quantitative segmentation of foveal hypoplasia using handheld OCT, versus preferential looking (PL), as predictors of future vision in preverbal children with infantile nystagmus.
Longitudinal cohort study.
Forty-two patients with infantile nystagmus (19 with albinism, 17 with idiopathic infantile nystagmus, and 6 with achromatopsia) were examined.
Spectral-domain handheld OCT was performed in preverbal children up to 36 months of age. Foveal tomograms were graded using our 6-point grading system for foveal hypoplasia and were segmented for quantitative analysis: photoreceptor length, outer segment (OS) length, and foveal developmental index (FDI; a ratio of inner layers versus total foveal thickness). Patients were followed up until they could perform chart visual acuity (VA) testing. Data were analyzed using linear mixed regression models. Visual acuity predicted by foveal grading was compared with prediction by PL, the current gold standard for visual assessment in infants and young children.
Grade of foveal hypoplasia, quantitative parameters (photoreceptor length, OS length, FDI), and PL VA were obtained in preverbal children for comparison with future chart VA outcomes.
We imaged 81 eyes from 42 patients with infantile nystagmus of mean age 19.8 months (range, 0.9-33.4 months; standard deviation [SD], 9.4 months) at the first handheld OCT scan. Mean follow-up was 44.1 months (range, 18.4-63.2 months; SD, 12.0 months). Structural grading was the strongest predictor of future VA (grading: r = 0.80, F = 67.49, P < 0.0001) compared with quantitative measures (FDI: r = 0.74, F = 28.81, P < 0.001; OS length: r = 0.65; F = 7.94, P < 0.008; photoreceptor length: r = 0.65; F = 7.94, P < 0.008). Preferential looking was inferior to VA prediction by foveal grading (PL: r = 0.42, F = 3.12, P < 0.03).
Handheld OCT can predict future VA in infantile nystagmus. Structural grading is a better predictor of future VA than quantitative segmentation and PL testing. Predicting future vision may avert parental anxiety and may optimize childhood development.

The optimal management of infantile nystagmus syndrome (INS) is still unclear. Contact lenses (CL) may be superior to glasses in improving visual function in INS but it is not known whether their beneficial effects are due to optical correction alone, or to an additional proprioceptive effect, and whether soft CLs would be as effective as rigid CLs. There is little data on feasibility and and the present study aimed to provide this information.
We completed a pilot Randomized Control Trial (RCT) at a single tertiary referral centre in London, UK. We enrolled 38 adults with idiopathic INS and randomised them to either plano CL (with corrective spectacles if required) or to corrective CL. CL wear was required for a minimum of 2 weeks. Primary outcome measures were feasibility and safety of CL wear in INS; secondary outcome measures were visual acuity and nystagmus waveform parameters.
27 completed the study (27/38,71%). 4 partcipants withdrew due to difficulty with CL insertion/removal and 7 were lost to follow up. CL tolerability was high (24/27,89%) - 2 found the CLs irritant, and 1 had an exacerbation of allergic eye disease. At two weeks, mean improvement in binocular visual acuity from baseline with plano CLs was 0.07 logMAR (95% confidence interval (CI: 0.03-0.11) and 0.06 logMAR with fully corrective CLs (95% CI:0.02-0.1). Mean improvement in the eXpanded Nystagmus Acuity Function (NAFX, a nystagmus acuity function based on eye movement recording) with plano CLs was -0.04(95% CI: -0.08-0.005) and -0.05 with fully corrective CLs(95% CI: -0.09-0.003).
CLs are well tolerated, with a low risk profile. Whilst our study was not powered to detect significant changes in BCVA and waveform parameters between treatment arms, we observed a trend towards an improvement in visual function at two weeks from baseline with CLs.

OBJECTIVE: To evaluate the effect of treatment with topical brinzolamide on visual acuity and nystagmus intensity in patients with congenital nystagmus.
METHODS: A retrospective study was designed in which the clinical records of 14 patients with congenital nystagmus were reviewed. All patients underwent a complete ophthalmological examination and a Perea video-oculography (VOG) before, and three days after, initiation of treatment with topical brinzolamide (Azopt). Five expert researchers evaluated the intensity of nystagmus by video before and after treatment. Finally, the subjective improvement of the patients was recorded.
RESULTS: Statistically significant differences were found in pre- and post-treatment binocular near visual acuity. A slight increase in the frequency of nystagmus was found, which was statistically significant with the horizontal gaze to the left and with the gaze downwards (P=.04, P=.03, respectively). The kappa index concordance between the researchers evaluating the intensity of nystagmus was 0.014. Only two of the patients noticed improvement in visual acuity, and one patient noticed improvement in the aesthetic aspect.
CONCLUSIONS: In spite of an improvement in nystagmus, it was slight, not cosmetically appreciable by patients in most cases, and was not related to a significant improvement in visual acuity or in patient quality of life. Further studies are needed to evaluate the effects of topical brinzolamide, and to establish potential therapeutic indications in nystagmus.

OBJECTIVE: To perform the first randomized controlled trial comparing soft contact lens (SCL) with rigid gas-permeable lens (RGPL) wearing in infantile nystagmus (IN), using spectacle wear as a baseline.
METHODS: Randomized, controlled cross-over trial with an intention-to-treat design.
METHODS: A total of 24 participants with IN (12 idiopathic, 12 with albinism).
METHODS: Participants were randomized into 1 of 2 treatment arms receiving the following sequence of treatments (2-3 weeks for each treatment): (A) spectacles, SCL, RGPL, and spectacle wear; or (B) spectacles, RGPL, SCL, and spectacle wear.
METHODS: The main outcome measure was mean intensity of nystagmus at the null region viewing at 1.2 m. Secondary outcome measures included the same measure at 0.4 m viewing and across the horizontal meridian (measured over a ±30° range at 3° intervals) for distance and near. The nystagmus foveation characteristics were similarly assessed over ±30° and at the null region at 1.2 m and 0.4 m viewing. Visual outcome measures included best-corrected visual acuity (BCVA) at 4 m and 0.4 m, gaze-dependent visual acuity (GDVA) (i.e., visual acuity when maintaining gaze angles over a ±30° range at 10° intervals) at 4 m, and reading performance at 0.4 m derived from the Radner reading chart.
RESULTS: There were no significant differences between SCL and RGPL wearing for any nystagmus characteristics or compared with spectacle wearing. The BCVA, reading acuity, and critical print size were significantly worse for SCL wearing compared with RGPL and baseline spectacle wear (P<0.05), although mean differences were less than 1 logarithm of the minimum angle of resolution (logMAR) line.
CONCLUSIONS: Nystagmus was not significantly different during SCL and RGPL wearing in IN, and contact lens wearing does not significantly reduce nystagmus compared with baseline spectacle wearing. The wearing of SCL leads to a small but statistically significant deterioration in visual function compared with both RGPL and spectacle wearing at baseline, although mean effect sizes were not clinically relevant.

OBJECTIVE: To explore the onset and progression of spherical refractive error in a population with infantile nystagmus syndrome.
METHODS: Retrospective refractive error data were obtained from 147 medical records of children with infantile nystagmus syndrome (albinism n = 98; idiopathic infantile nystagmus n = 49), attending a low vision clinic in Northern Ireland, over a 24 year period (1986-2010). Data were categorised by age to allow for comparisons with published studies. A prospective group of participants with Infantile nystagmus syndrome (INS) [n = 22 (albinism n = 18, idiopathic infantile nystagmus n = 4)] (aged 0-4) were also recruited. Cycloplegic streak retinoscopy was performed biannually, over a 3 year period. Spherical equivalent refractive error and most ametropic meridian were analysed.
RESULTS: The mean spherical equivalent refractive errors for albinism and idiopathic infantile nystagmus groups (across all age categories) were hypermetropic, with highest levels demonstrated by the participants with albinism aged 1 ≤ 4 years (Mann-Whitney U test, p = 0.013). Mean most ametropic meridian was highest in the albinism group aged 1 ≤ 12 years (Mann-Whitney U test, p < 0.05). Individual data demonstrated relatively static spherical equivalent refractive errors over time. Prospective participants were hypermetropic at all visits and those with albinism had, on average, higher refractive errors than those with idiopathic infantile nystagmus (IIN). No significant correlations were noted between visual acuity and spherical equivalent refractive errors or most ametropic meridian.
CONCLUSIONS: Hypermetropia is the most prevalent spherical refractive error in the INS population, irrespective of level of visual acuity. Individuals with infantile nystagmus syndrome fail to demonstrate typical patterns of emmetropisation, particularly in the presence of albinism.

OBJECTIVE: To study the disease-causing gene for a Chinese family with X-linked congenital idiopathic nystagmus.
METHODS: It was a retrospective study. The phenotype of a Chinese family with congenital nystagmus was identified by investigating the history and the clinical features of each family member. The mode of inheritance in this family was ascertained by the pedigree analysis. Linkage analysis was performed to identify the possible locus harboring the disease-causing gene. Direct DNA sequence analysis was performed to find the mutation responsible for this disease.
RESULTS: The positive LOD score was obtained for 10 microsatellite makers on chromosome Xq25-Xq27, and the maximum LOD score with DXS1211 was 3.91. A 2-bp deletion in exon 8 of FRMD7 was detected after direct DNA sequence analysis, which was cosegregated with all patients in this family.
CONCLUSIONS: Congenital nystagmus is a clinically and genetically heterogeneous ocular movement disease. Mutation of the FRMD7 gene is the cause of congenital nystagmus in this family.