Inclusive Fitness May Explain Some but Not All Benefits Derived from Helping Behavior in a Cooperatively Breeding Bird.

AbstractIn cooperative breeding systems, inclusive fitness theory predicts that nonbreeding helpers more closely related to the breeders should be more willing to provide costly alloparental care and thus have more impact on breeder fitness. In the red-cockaded woodpecker (Dryobates borealis), most helpers are the breeders' earlier offspring, but helpers do vary within groups in both relatedness to the breeders (some even being unrelated) and sex, and it can be difficult to parse their separate impacts on breeder fitness. Moreover, most support for inclusive fitness theory has been positive associations between relatedness and behavior rather than actual fitness consequences. We used functional linear models to evaluate the per capita effects of helpers of different relatedness on eight breeder fitness components measured for up to 41 years at three sites. In support of inclusive fitness theory, helpers more related to the breeding pair made greater contributions to six fitness components. However, male helpers made equal contributions to increasing prefledging survival regardless of relatedness. These findings suggest that both inclusive fitness benefits and other direct benefits may underlie helping behaviors in the red-cockaded woodpecker. Our results also demonstrate the application of an underused statistical approach to disentangle a complex ecological phenomenon.

Outcomes of Strabismus Surgery Following Teprotumumab Therapy.

PURPOSE: To investigate the results of patients undergoing surgical treatment for strabismic diplopia in thyroid eye disease (TED) following teprotumumab. DESIGN: Multicenter, retrospective, case series. METHODS: We report 28 patients who underwent extraocular muscle surgery for strabismic diplopia after treatment with teprotumumab at 7 different academic centers. Elapsed time from last teprotumumab dose to the date of surgery, previous orbital decompression, primary preoperative horizontal and vertical deviation, surgical procedure, and 2-month postoperative results were collected from the patient records. RESULTS: Sixteen (57%) patients were diplopia-free after 1 surgery. Three (11%) chose prism spectacles to correct residual diplopia, 2 (7%) used compensatory head posture to resolve diplopia, and 1 (4%) had intermittent diplopia and was functionally improved (choosing no prisms or further surgery). These were considered treatment successes. Three (11%) patients required reoperation, and all were diplopia-free after their second procedure. CONCLUSIONS: Most patients requiring surgery for strabismic diplopia following teprotumumab achieve good outcomes with success rates comparable to series published before the availability of teprotumumab.

Larger workers outperform smaller workers across resource environments: An evaluation of demographic data using functional linear models.

Behavior and organization of social groups is thought to be vital to the functioning of societies, yet the contributions of various roles within social groups toward population growth and dynamics have been difficult to quantify. A common approach to quantifying these role-based contributions is evaluating the number of individuals conducting certain roles, which ignores how behavior might scale up to effects at the population-level. Manipulative experiments are another common approach to determine population-level effects, but they often ignore potential feedbacks associated with these various roles.Here, we evaluate the effects of worker size distribution in bumblebee colonies on worker production in 24 observational colonies across three environments, using functional linear models. Functional linear models are an underused correlative technique that has been used to assess lag effects of environmental drivers on plant performance. We demonstrate potential applications of this technique for exploring high-dimensional ecological systems, such as the contributions of individuals with different traits to colony dynamics.We found that more larger workers had mostly positive effects and more smaller workers had negative effects on worker production. Most of these effects were only detected under low or fluctuating resource environments suggesting that the advantage of colonies with larger-bodied workers becomes more apparent under stressful conditions.We also demonstrate the wider ecological application of functional linear models. We highlight the advantages and limitations when considering these models, and how they are a valuable complement to many of these performance-based and manipulative experiments.

Identification of Evidence for Key Positive Psychological Constructs in Pediatric and Adolescent/Young Adult Patients with Cancer: A Scoping Review.

Introduction: Children and adolescents/young adults (AYAs) with cancer are a vulnerable population susceptible to numerous late effects, such as fatigue and depression, which may diminish their long-term psychological, physical, spiritual, and emotional health. A well-rounded understanding of how positive psychological constructs affect the quality of care and treatment outcomes is therefore warranted. Methods: We conducted a scoping review of 15 positive psychological constructs in children and AYAs with cancer. The primary research questions were (1) what is known about positive psychological constructs in children and AYAs with cancer; (2) what value is ascribed to these constructs by patients? Results: Two hundred seventy-six articles were included after database search and screening. These studies were mostly observational or qualitative and conducted in North America. Constructs were often poorly defined, and measurement tools used to gather data were wide ranging. Numerous factors were correlated with increased or decreased expression of certain constructs, but overall themes were difficult to identify. Similarly, patients often spoke of what increased or decreased expression of a construct, with less emphasis on what they implicitly value. Discussion: This scoping review found ample evidence for what increases or decreases expression of positive psychological constructs, but this evidence was observational and often conflicting. In the future, we recommend the development of a core set of psychological outcomes, with definitions and corresponding measurement tools. We further recommend an emphasis on randomized trials to more rigorously study how expression of constructs can be improved and what effect this has on the quality of life.

Effect of Age at Primary Intraocular Lens Implantation on Refractive Growth in Young Children.

PURPOSE: To evaluate the effect of age at primary intraocular lens (IOL) implantation on rate of refractive growth (RRG3) during childhood. METHODS: A retrospective chart review was performed for children undergoing primary IOL implantation during cataract surgery. RRG3 was calculated for one eye from each patient using the first postoperative refraction, last refraction that remained stable (< 1.00 diopters [D] change/2 years), and the corresponding ages. RRG3 values for pseudophakic patients operated on from ages 0 to 5 months were compared with values for patients operated on at ages 6 to 23 months and 24 to 72 months. Patients with refractive errors that stabilized were grouped by age at surgery to compare age at refractive plateau. RESULTS: Of 296 eyes identified from 219 patients, 46 eyes met the inclusion criteria. There was a statistically significant difference in RRG3 among age groups. The mean RRG3 value was -19.82 ± 5.23 D for the 0 to 5 months group, -22.32 ± 7.45 D for the 6 to 23 months group (0 to 5 months vs 6 to 23 months, P = .43), and -9.64 ± 11.95 D for the 24 to 72 months group (0 to 5 months vs 24 to 72 months, P = .01). CONCLUSIONS: Age at primary IOL implantation affects the RRG3, especially for children 0 to 23 months old at surgery. Surgeons performing primary IOL implantation in infants may want to use age-adjusted assumptions, because faster refractive growth rates can be expected in young children. [J Pediatr Ophthalmol Strabismus. 2020;57(4):264-270.].

Unilateral Abducens Nerve Palsy Following Perinatal Stroke of the Middle Cerebral Artery.

The authors describe a case of unilateral abducens nerve palsy following perinatal stroke of the middle cerebral artery. A 1-year-old boy presented with left eye esotropia but no other ocular abnormalities. The patient's history, examination, and diagnostic tests were consistent with abducens nerve palsy. He underwent left medial rectus recession of 5.5 mm and left lateral rectus resection of 7 mm followed by patching. At 15 months after surgery, primary gaze by prism alternate cover testing revealed a 4 prism diopter (PD) esophoria (small angle in left gaze with essentially no action of lateral rectus) and 2 PD right hyperphoria. Ophthalmologic management of abducens nerve palsy entails addressing neurological sequelae in a timely manner, treating the esotropia and strabismic amblyopia to optimize visual system development. [J Pediatr Ophthalmol Strabismus. 2020;57:e30-e33.].

Developmental trap or demographic bonanza? Opposing consequences of earlier phenology in a changing climate for a multivoltine butterfly.

A rapidly changing climate has the potential to interfere with the timing of environmental cues that ectothermic organisms rely on to initiate and regulate life history events. Short-lived ectotherms that exhibit plasticity in their life history could increase the number of generations per year under warming climate. If many individuals successfully complete an additional generation, the population experiences an additional opportunity to grow, and a warming climate could lead to a demographic bonanza. However, these plastic responses could become maladaptive in temperate regions, where a warmer climate could trigger a developmental pathway that cannot be completed within the growing season, referred to as a developmental trap. Here we incorporated detailed demography into commonly used photothermal models to evaluate these demographic consequences of phenological shifts due to a warming climate on the formerly widespread, multivoltine butterfly (Pieris oleracea). Using species-specific temperature- and photoperiod-sensitive vital rates, we estimated the number of generations per year and population growth rate over the set of climate conditions experienced during the past 38 years. We predicted that populations in the southern portion of its range have added a fourth generation in recent years, resulting in higher annual population growth rates (demographic bonanzas). We predicted that populations in the Northeast United States have experienced developmental traps, where increases in the thermal window initially caused mortality of the final generation and reduced growth rates. These populations may recover if more growing degree days are added to the year. Our framework for incorporating detailed demography into commonly used photothermal models demonstrates the importance of using both demography and phenology to predict consequences of phenological shifts.

Congenital Ocular Neuromyotonia with Partial Third Nerve Palsy.

PURPOSE: We report the first case of congenital ocular neuromyotonia (ONM) and the results of strabismus surgery for this patient's co-existing cranial nerve (CN) III palsy. PATIENTS AND METHOD: The patient presented at 18 months with strabismus that had reportedly been present since the time of birth. On exam, she had persistent exotropia (RXT) and hypertropia (RHT) with episodes of esotropia in the right eye that could be evoked by sustained left gaze. A diagnosis of ONM with partial CN III palsy was made. T1-weighted, T2-weighted, and fluid-attenuated inversion recovery magnetic resonance imaging failed to reveal intracranial pathology. RESULTS: Gaze induced intermittent esotropia resolved with carbamazepine. Surgery was performed to improve the patient's RXT and RHT. Post-operatively, the patient's RXT had improved from 12 to 15 prism diopters (∆) at near and 20∆ at a distance to 10∆ RXT at near with no horizontal deviation at distance. Her deviation has remained stable for 13 years, as has her neurological exam and good state of health. CONCLUSION: This case demonstrates that ONM may present congenitally and adds to the body of knowledge regarding surgical outcomes on concurrent CN palsies in these patients.

Lateral rectus muscle resection following maximal recession of the medial rectus muscle in thyroid eye disease.

BACKGROUND: Rectus muscle restriction is a common finding in thyroid eye disease (TED). Typically, restricted muscles are recessed to address strabismus and diplopia. However, some patients have residual strabismus following maximal recession of a restricted muscle. The purpose of this study was to report outcomes following resection of the lateral rectus muscle after maximal recession of the medial rectus muscle in patients with TED. METHODS: The medical records of patients with TED who underwent lateral rectus resection between 1998 and 2015 were reviewed retrospectively. Information regarding thyroid disease history and surgical treatment, including history of orbital decompressions, rectus muscle recessions, rectus muscle resections, and pre- and postoperative alignment was collected. Adjustable suture was used in all cases. Success was defined as a postoperative orthotropia with ≤2Δ of phoria at distance and a phoria at near. RESULTS: A total of 11 patients were included. Of these, 10 (91%) required postoperative adjustment. A successful outcome was achieved in 10 cases (91%). CONCLUSIONS: Lateral rectus muscle resection to address residual esotropia and diplopia was effective at reducing residual esotropia following medial rectus recession in our study cohort.

Prioritizing management actions for invasive populations using cost, efficacy, demography and expert opinion for 14 plant species world-wide.

Management of invasive populations is typically investigated case-by-case. Comparative approaches have been applied to single aspects of management, such as demography, with cost or efficacy rarely incorporated.We present an analysis of the ranks of management actions for 14 species in five countries that extends beyond the use of demography alone to include multiple metrics for ranking management actions, which integrate cost, efficacy and demography (cost-effectiveness) and managers' expert opinion of ranks. We use content analysis of manager surveys to assess the multiple criteria managers use to rank management strategies.Analysis of the matrix models for managed populations showed that all management actions led to reductions in population growth rate (λ), with a median 48% reduction in λ across all management units; however, only 66% of the actions led to declining populations (λ < 1).Each management action ranked by cost-effectiveness and cost had a unique rank; however, elasticity ranks were often tied, providing less discrimination among management actions. Ranking management actions by cost alone aligned well with cost-effectiveness ranks and demographic elasticity ranks were also well aligned with cost-effectiveness. In contrast, efficacy ranks were aligned with managers' ranks and managers identified efficacy and demography as important. 80% of managers identified off-target effects of management as important, which was not captured using any of the other metrics. Synthesis and applications. A multidimensional view of the benefits and costs of management options provides a range of single and integrated metrics. These rankings, and the relationships between them, can be used to assess management actions for invasive plants. The integrated cost-effectiveness approach goes well 'beyond demography' and provides additional information for managers; however, cost-effectiveness needs to be augmented with information on off-target effects and social impacts of management in order to provide greater benefits for on-the-ground management.

Orbital Metastasis Is Associated With Decreased Survival in Stage M Neuroblastoma.

BACKGROUND: Approximately 30% of patients with metastatic (stage M) neuroblastoma present with periorbital ecchymosis from orbital osseous disease. Though locoregional disease is staged by imaging, the prognostic significance of metastatic site in stage M disease is unknown. We hypothesize that, compared to nonorbital metastasis, orbital metastasis is associated with decreased survival in patients with stage M neuroblastoma, and that periorbital ecchymosis reflects location and extent of orbital disease. PROCEDURE: Medical records and imaging from 222 patients with stage M neuroblastoma seen at St. Jude Children's Research Hospital between January 1995 and May 2009 were reviewed. Thirty-seven patients were <18 months of age at diagnosis and 185 were ≥18 months of age. Overall survival (OS) and 5-year survival (5YS) were compared for patients with and without orbital, calvarial and nonorbital osseous metastasis, and with and without periorbital ecchymosis (log-rank test). Associations of periorbital ecchymosis with orbital metastasis location/extent were explored (Fisher's exact test, t-test). RESULTS: In patients ≥18 months of age, only orbital metastasis was associated with decreased 5YS (P = 0.0323) and OS (P = 0.0288). In patients <18 months of age, neither orbital, calvarial, or nonorbital bone metastasis was associated with OS or 5YS. Periorbital ecchymosis was associated with higher number of involved orbital bones (P = 0.0135), but not location or survival. CONCLUSIONS: In patients ≥ 18 months of age with stage M neuroblastoma, orbital metastatic disease is associated with decreased 5YS and OS. In future clinical trials, orbital disease may be useful as an imaging-based risk factor for substratification of stage M neuroblastoma.

Characterization of a Case of Pigmentary Retinopathy in Sanfilippo Syndrome Type IIIA Associated with Compound Heterozygous Mutations in the SGSH Gene.

PURPOSE: To report longitudinal phenotypic findings in a patient with Sanfilippo syndrome type IIIA, harboring SGSH mutations, one of which is novel. METHODS: Heparan-N-sulfatidase enzyme function testing in skin fibroblasts and white blood cells and SGSH gene sequencing were obtained. Clinical office examinations, examinations under anesthesia, electroretinogram, spectral domain optical coherence tomography (SD-OCT), and fundus photography were performed over a 5-year period. RESULTS: Fundus examination revealed a progressive breadcrumb-like pigmentary retinopathy with perifoveal pigmentary involvement. SD-OCT showed loss of normal neuroretinal lamination and cystic macular changes responsive to treatment with carbonic anhydrase inhibitors. Electroretinography exhibited complex characteristics indicative of a generalized retinal rod > cone dysfunction with significant ON > OFF postreceptoral response compromise. Sequencing revealed compound heterozygous mutations in the SGSH gene, the novel c.88G > C (p.A30P) change and a second, previously reported one (c.734G > A, p.R245H). CONCLUSIONS: We have identified ocular features of a patient with Sanfilippo syndrome type IIIA harboring a novel SGHS mutation that were not previously known to occur in this disease - namely, a progressive retinopathy with distinctive features, cystic macular changes responsive to carbonic anhydrase inhibitors, and complex electroretinographic abnormalities consistent with postreceptoral dysfunction. SD-OCT imaging revealed retinal lamination changes consistent with previously reported histologic studies. Both the SD-OCT and the electroretinogram changes appear attributable to intraretinal deposition of heparan sulfate.

Establishing a surgical outreach program in the developing world: pediatric strabismus surgery in Guatemala City, Guatemala.

PURPOSE: To report our experince in establishing a sustainable pediatric surgical outreach mission to an underserved population in Guatemala for treatment of strabismic disorders. METHODS: A pediatric ophthalmic surgical outreach mission was established. Children were evaluated for surgical intervention by 3 pediatric ophthalmologists and 2 orthoptists. Surgical care was provided at the Moore Pediatric Surgery Center, Guatemala City, over 4 days. Postoperative care was facilitated by Guatemalan physicians during the second year. RESULTS: In year 1, patients 1-17 years of age were referred by local healthcare providers. In year 2, more than 60% of patients were prescreened by a local pediatric ophthalmologist. We screened 47% more patients in year 2 (132 vs 90). Diagnoses included congenital and acquired esotropia, consecutive and acquired exotropia, congenital nystagmus, Duane syndrome, Brown syndrome, cranial nerve palsy, dissociated vertical deviation, and oblique muscle dysfunction. Overall, 42% of the patients who were screened underwent surgery. We performed 21 more surgeries in our second year (58 vs 37), a 57% increase. There were no significant intra- or postoperative complications. CONCLUSIONS: Surgical outreach programs for children with strabismic disorders in the developing world can be established through international cooperation, a multidisciplinary team of healthcare providers, and medical equipment allocations. Coordinating care with local pediatric ophthalmologists and medical directors facilitates best practice management for sustainability.

Residual Strabismus in Children Following Improvement of Cranial Nerve Palsies Affecting Ocular Ductions.

BACKGROUND: Children with brain neoplasms often develop cranial nerve palsies (CNP) affecting ocular ductions. Duction deficits may improve or resolve with treatment of their intracranial disease. However, these children may be left with residual strabismus. METHODS: We identified 104 children with third, fourth, and/or sixth cranial nerve palsies who were treated for central nervous system (CNS) neoplasms. A retrospective chart review was conducted to determine the presence or absence of residual strabismus following resolution of duction deficits. RESULTS: Of the 104 children with CNP secondary to an intracranial neoplasm, forty-five had improvement or resolution of their duction deficit with treatment of their CNS lesion. Of these forty-five children, one had a third cranial nerve palsy, six had fouth cranial nerve palsies (one was bilateral), thirty-seven had sixth cranial nerve palsies (thirteen were bilateral), and one had two different cranial nerve palsies in the same eye (fourth and sixth). Of the eighteen children with improved (but not resolved) duction deficits, only three (17%) experienced resolution of their strabismus. Of the twenty-seven children with resolved duction deficits, nine (33%) experienced resolution of their strabismus. For the children with residual strabismus, the average angle of strabismus before duction deficits improved or resolved was 33.2Δ; while for those children without residual strabismus, it was 20Δ. CONCLUSIONS: Our findings indicated that the majority of children with improved or resolved duction deficits from CNP after treatment for CNS neoplasms are left with residual strabismus. Therefore, we suggest children with CNP secondary to CNS neoplasms need ophthalmic care after duction deficits resolve, as they are likely to have residual strabismus.

Traumatic avulsion of the oculomotor nerve documented by high-resolution magnetic resonance imaging.

Autopsy studies have described definitive traumatic avulsion of the oculomotor nerve from the brainstem; however, detailed characterization of mechanisms and localization of traumatic nerve injury has yet to be definitively described in vivo. We report the case of a 13-year-old girl in whom high-resolution magnetic resonance imaging confirmed irreversible injury to the left oculomotor nerve after trauma.

Postoperative shift in ocular alignment following single vertical rectus recession on adjustable suture in adults without thyroid eye disease.

PURPOSE: To determine whether overcorrection shifts occur after vertical rectus recession on adjustable suture in the absence of thyroid eye disease. METHODS: The medical records of patients without thyroid eye disease who underwent vertical rectus recession surgery from 2001 to 2008 were retrospectively reviewed for shifts in alignment between suture adjustment at postoperative day 1 and 2 months' follow-up. Superior rectus and inferior rectus recessions were compared. In addition, we compared the use of a nonabsorbable polyester suture to an absorbable polyglactin 910 suture in nonthyroid patients undergoing inferior rectus recessions. RESULTS: A total of 59 patients were included (superior rectus, 30; inferior rectus, 29). We found a mean undercorrection shift of 1.1 (range, 17.5(Δ) undercorrection to 16(Δ) overcorrection) and 1.0(Δ) (range, 12(Δ) undercorrection shift to 6(Δ) overcorrection shift) for superior and inferior rectus recessions, respectively, between 1 day and 2 months postoperatively. CONCLUSIONS: There was no trend toward overcorrection following unilateral vertical rectus adjustable suture recessions in patients without thyroid eye disease, suggesting that thyroid myopathy may account for overcorrection shifts seen with this surgery.

Abnormal cone ERGs in a family with congenital nystagmus and photophobia harboring a p.X423Lfs mutation in the PAX6 gene.

PURPOSE: To describe the clinical, functional, and genetic findings in a young Caucasian girl and her father, in whom a mutation of the PAX6 gene was identified. METHODS: Detailed histories, eye examinations, and flash electroretinograms (ERGs) were acquired from both patients, and molecular genetic diagnostic testing was performed. Both patients were followed over a 2-year period. RESULTS: At presentation, the proband displayed congenital nystagmus, photophobia, posterior embryotoxon, foveal hypoplasia, and coarse peripheral retinal pigment epithelium mottling. Light-adapted cone-driven ERG responses were delayed and reduced. The father had similar findings, but additionally displayed corneal clouding and pannus, decreased best-corrected visual acuity, and his ERG demonstrated a larger reduction in ERG cone-driven responses. PAX6 testing of the proband revealed a heterozygous mutation in exon 13 resulting in a p.X423Lfs (p.Stop423Leufs) frameshift amino acid substitution, predicting aberrant protein elongation by either 14 or 36 amino acids (p.X423Lext14 or p.X423Lext36) and subsequent disruption of normal protein function. CONCLUSIONS: The p.X423Lfs mutation has previously been described in cases of atypical aniridia, but this is the first report demonstrating abnormal cone-driven ERG responses associated with this particular mutation of the PAX6 gene. ERG abnormalities have been documented in other mutations of the PAX6 gene, and we propose that the retinal pathology causing these ERG abnormalities may contribute to the photophobia experienced by patients with aniridia. Systematic ERG testing can aid in the diagnosis of PAX6-related disorders and may prove to be a useful tool to objectively assess responses to future treatments.

Persistent binocular diplopia in childhood following successful treatment for esotropia: a case series.

INTRODUCTION: Diplopia is rare in children with nonpathological esotropia because facultative suppression develops prior to visual maturation. Our aim is to present five cases of children with binocular diplopia following treatment of childhood esotropia, exploring possible mechanisms for the development of diplopia based upon the patient's history and findings, and discussing treatment for diplopia in this setting. METHODS: A retrospective chart review of five sequential patients presenting with binocular diplopia following treatment of esotropia was performed. Treatment of esotropia included correction of hyperopic error, correction of anisometropic amblyopia to 20/30 or better, and strabismus surgery as indicated. RESULTS: Diplopia developed in two children with accommodative esotropia, one child with infantile esotropia and partially accommodative esotropia, and two children with a history of infantile esotropia and consecutive exotropia following surgical correction. Diplopia onset occurred between ages 7 and 11. Four of the five children experienced resolution of diplopia with prism glasses. CONCLUSION: Children with esotropia before visual maturation may develop persistent diplopia. Clinical features of the children with diplopia in our case series include poor fusion, poor stereopsis, consecutive exotropia, refractive changes, onset of diplopia after 7 years of age, and occlusion therapy for amblyopia. Prisms may be beneficial in controlling the diplopia.

Phenotypic expression of Bardet-Biedl syndrome in patients homozygous for the common M390R mutation in the BBS1 gene.

PURPOSE: To characterize the phenotype of Bardet-Biedl syndrome (BBS) patients homozygous for the BBS1 M390R mutation. METHODS: Three patients [PT1, F, 27 years old (yo) at last examination, 14-year follow-up (F/U) PT2, F, 15-yo PT3, M, 15-yo, both 1-year F/U] underwent eye exams, Goldmann visual fields (GVFs), dark- (DA) and light-adapted (LA) electroretinograms (ERGs), spectral domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF). Vision and systemic history were also collected. RESULTS: All patients had night blindness, hyperopic astigmatism, ptosis or mild blepharospasm, foot polydactyly, 5th finger clinodactyly, history of headaches, and variable, diet-responsive obesity. Two had asthma, PT1 was developmentally delayed, PT2 had Asperger-like symptoms, and PT3 had normal cognition. At age 14, acuity was 20/100 in PT1, who had nystagmus since age 2, 20/40 in PT2 and 20/30 in PT3. By 27yo PT1 progressed to 20/320, by 15 yo PT2 was 20/60 and PT3 remained stable. PT1 had well preserved peripheral GVFs, with minimal progression over 10 years of F/U. PT2 and PT3 presented with ring scotomas and I4e<5°. All patients had severe generalized visual sensitivity depression. ERGs were consistently recordable (also rod ERG in PT3 after 60 min DA), but progressed to non-recordable in PT1. Mixed DA ERGs exhibited electronegativity. In PT3, this was partly due to a bleaching effect during bright-flash DA averaging, partly to ON≫OFF LA response compromise. PT2 and 3 had, on SD-OCTs, generalized macular thinning, normal retinal lamination, and widespread photoreceptor outer/inner segment attenuation except foveally, and multiple rings of abnormal FAF configuring a complex bull's eye-pattern. PT1 had macular atrophy. All patients also had peripapillary nerve fiber layer thickening. CONCLUSIONS: The observed phenotype matches very closely that reported in patients by Azari et al. (IOVS 2006) and in the Bbs1-M390R knock-in mouse model, and expands it to the characterization of important ERG response characteristics that provide insight in the pathogenesis of retinopathy in these patients. Our findings confirm the consistent pathogenicity of the BBS1 M390R mutation.