Low-dose AtropIne for Myopia Control in Children (AIM): protocol for a randomised, controlled, double-blind, multicentre, clinical trial with two parallel arms.

INTRODUCTION: Myopia is a major cause of degenerative eye disease and increases the risk of secondary visual impairment. Mitigating its progression therefore has great potential of clinically relevant benefit as shown by using highly diluted atropine eye drops in children of Asian origin. However, limited evidence is available regarding the efficacy and safety of low-dose atropine therapy in non-Asian populations. Hence, the Low-dose AtropIne for Myopia Control in Children (AIM) study will test the efficacy and safety of 0.02% atropine vs placebo in a German population. METHODS AND ANALYSIS: AIM is a national, multicentre, prospective, randomised, placebo-controlled, double-blind trial with two parallel arms. The primary objective is to assess the efficacy of atropine 0.02% eyedrops for myopia control in children of Caucasian origin. The primary outcome is the change in cycloplegic refraction after 1 year of treatment (D/year). Secondary and tertiary outcome measures comprise the change in axial length (mm/year) in children treated with 0.02% atropine compared with placebo, the myopic progression of participants treated with 0.01% compared with 0.02% atropine (D/year and mm/year), and the safety profile of both 0.02% and 0.01% atropine. Furthermore, the myopic progression 1 year after cessation of therapy with 0.02% atropine will be evaluated. Inclusion criteria are an age of 8-12 years and myopia of -1 D to -6 D with an estimated annual myopia progression of ≥0.5 D. After randomisation, patients will receive either atropine 0.02% (arm A) or placebo eye drops (arm B) in the first year of treatment. In the second year, they will continue to receive atropine 0.02% (arm A) or switch to atropine 0.01% (arm B). In the third year, they will switch to placebo (arm A) or continue with atropine 0.01% (arm B). To achieve a statistical power of 80%, the calculated sample size is 300. The trial has started in October 2021 with a planned recruitment period of 18 months. ETHICS AND DISSEMINATION: AIM has been approved by the Central Ethics Committee of the University Medical Center Freiburg (21-1106), local ethics committees of each participating centre and the German Federal Institute for Drugs and Medical Devices (61-3910-4044659). It complies with the Declaration of Helsinki, local laws and ICH-GCP. Results and underlying data from this trial will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT03865160.

The influence of stereoscopic vision on surgical performance in minimal invasive surgery-a substudy of the IDOSP-Study (Influence of 3D- vs. 4 K-Display Systems on Surgical Performance in minimal invasive surgery).

PURPOSE: This study is a secondary analysis of the IDOSP trial published in the Annals of Surgery 2020. The aim of this study was to examine the influence of stereo acuity on surgical performance in a laparoscopic training parkour with 3D- versus 4 K-2D-display technique. METHODS: The surgical performance of medical students (MS), non-board-certified surgeons (NBC), and board-certified surgeons (BC) was compared using 3D- versus 4 K-2D-display technique at a training parkour in a randomized cross-over trial. Stereo acuity was tested by TNO and Titmus Stereo tests. RESULTS: Eighty-nine participants were included in this sub-trial. The median stereo acuity for all participants, measured with the Titmus test, was 25 s arc, with TNO test 30 s arc. Higher quality stereo vision, measured with the Titmus test, correlated significantly with a reduced parkour time (r = 0.26, p = 0.02) and error (r = 0.21, p = 0.048) with the 3D screen. The TNO test did not correlate significantly with parkour performance. There was no statistically significant correlation between parkour time nor error and stereo acuity using the 4 K system (p > 0.457 respectively). Higher age showed a significant correlation with lower stereo acuity measured with TNO (r = 0.21, p = 0.014), but not with the Titmus test (r = - 0.7, p = 0.39). Seven percent of the group "NBC and BC" showed reduced stereo acuity > 120 s arc with the Titmus test and 3% with the TNO test. CONCLUSION: High-quality stereo vision is of utmost importance for surgical skills using a 3D-display system. This was most obvious for MS and for tasks that place particularly high demands on hand-eye coordination. The Titmus test was more precise than the TNO test to predict the benefit of a 3D monitor system. Experience and fine motor skills could partly compensate for a poorer stereo acuity. TRIAL REGISTRATION: This trial was registered at clinicaltrials.gov (trial number: NCT03445429, registered February 26, 2018).

Prism adaptation test before strabismus surgery in patients with decompensated esophoria and decompensated microesotropia.

PURPOSE: To evaluate the effect of Prism adaptation test (PAT) on the angle of squint in decompensated esophoria (decEPH) and decompensated microesotropia (decMET). METHODS: In this single-center retrospective study we reviewed the medical records of patients with the diagnosis of decEPH or decMET, aged at least 12 years, who were treated by strabismus surgery for the first time. The maximum Angle of squint (AOS) for far (F) and near (N) fixation and PAT results before surgery, as well as AOS (F) and AOS (N) after surgery and results of binocular function tests were considered. PAT included wearing a prism based on the largest angle for over 60 min. RESULTS: 100 patients (mean age 37 ± 17 years) were included in the decEPH group, 82 patients (mean age 30 ± 13 years) in the decMET group. For decEPH, before surgery AOS was 25.5 ± 8.8 pdpt (F) and 23.5 ± 9.8 pdpt (N). During PAT the AOS increased significantly by 2.7 ± 4.3 to 28.2 ± 8.6 pdpt (F) and by 4.9 ± 4.5 to 28.3 ± 9.5 pdpt (N). Altogether, in 82% of decEPH patients AOS (F) and/ or AOS (N) in- or decreased by at least 3 pdpt. For decMET, before surgery AOS was 28.6 ± 10.8 pdpt for far (F) and 30.9 ± 11.8 pdpt for near fixation (N). During PAT the AOS increased significantly by 4.2 ± 5.8 to 32.5 ± 9.5 pdpt (F) and by 3.7 ± 6.1 to 34.4 ± 9.5 pdpt (N). Altogether, in 51% of decMET patients, AOS (F) and/ or AOS (N) increased by at least 10 pdpt, therefore more than 5° which would have been maximally expected from mictrotropia, or decreased by at least 3 pdpt. CONCLUSIONS: The Prism adaptation test (PAT) showed remarkable changes in AOS in both decEPH and decMET. In patients with decEPH, the preoperative assessment of the "true AOS" under PAT reflects a pivotal requirement for successful strabismus surgery, as 82% had dose relevant angle changes ≥ 3 pdpt. For patients with decMET the preoperative prism adaptation test is especially of diagnostic value, but also 51% of decMET patients had changes in AOS beyond the expected microtropic angle (≥ 10 pdpt) or even a dose relevant angle decrease (≥ 3pdpt).

Gender benefit in laparoscopic surgical performance using a 3D-display system: data from a randomized cross-over trial.

BACKGROUND: The use of 3D technique compared to high-resolution 2D-4K-display technique has been shown to optimize spatial orientation and surgical performance in laparoscopic surgery. Since women make up an increasing amount of medical students and surgeons, this study was designed to investigate whether one gender has a greater benefit from using a 3D compared to a 4K-display system. METHODS: In a randomized cross-over trial, the surgical performance of male and female medical students (MS), non-board certified surgeons (NBCS), and board certified surgeons (BCS) was compared using 3D- vs. 4K-display technique at a minimally invasive training parkour with multiple surgical tasks and repetitions. RESULTS: 128 participants (56 women, 72 men) were included. Overall parkour time in seconds was 3D vs. 4K for all women 770.7 ± 31.9 vs. 1068.1 ± 50.0 (p < 0.001) and all men 664.5 ± 19.9 vs. 889.7 ± 31.2 (p < 0.001). Regarding overall mistakes, participants tend to commit less mistakes while using the 3D-vision system, showing 10.2 ± 1.1 vs. 13.3 ± 1.3 (p = 0.005) for all women and 9.6 ± 0.7 vs. 12.2 ± 1.0 (p = 0.001) for all men. The benefit of using a 3D system, measured by the difference in seconds, was for women 297.3 ± 41.8 (27.84%) vs. 225.2 ± 23.3 (25.31%) for men (p = 0.005). This can be confirmed in the MS group with 327.6 ± 65.5 (35.82%) vs. 249.8 ± 33.7 (32.12%), p = 0.041 and in the NBCS group 359 ± 52.4 (28.25%) vs. 198.2 ± 54.2 (18.62%), p = 0.003. There was no significant difference in the BCS group. CONCLUSION: 3D laparoscopic display technique optimizes surgical performance compared to the 2D-4K technique for both women and men. The greatest 3D benefit was found for women with less surgical experience. As a possible result of surgical education, this gender specific difference disappears with higher grade of experience. Using a 3D-vision system could facilitate surgical apprenticeship, especially for women.

Biallelic mutations in L-dopachrome tautomerase (DCT) cause infantile nystagmus and oculocutaneous albinism.

Infantile nystagmus syndrome (INS) denominates early-onset, involuntary oscillatory eye movements with different etiologies. Nystagmus is also one of the symptoms in oculocutaneus albinism (OCA), a heterogeneous disease mainly caused by defects in melanin synthesis or melanosome biogenesis. Dopachrome tautomerase (DCT, also called TYRP2) together with tyrosinase (TYR) and tyrosin-related protein 1 (TYRP1) is one of the key enzymes in melanin synthesis. Although DCT´s role in pigmentation has been proven in different species, until now only mutations in TYR and TYRP1 have been found in patients with OCA. Detailed ophthalmological and orthoptic investigations identified a consanguineous family with two individuals with isolated infantile nystagmus and one family member with subtle signs of albinism. By whole-exome sequencing and segregation analysis, we identified the missense mutation c.176G > T (p.Gly59Val) in DCT in a homozygous state in all three affected family members. We show that this mutation results in incomplete protein maturation and targeting in vitro compatible with a partial or total loss of function. Subsequent screening of a cohort of patients with OCA (n = 85) and INS (n = 25) revealed two heterozygous truncating mutations, namely c.876C > A (p.Tyr292*) and c.1407G > A (p.Trp469*), in an independent patient with OCA. Taken together, our data suggest that mutations in DCT can cause a phenotypic spectrum ranging from isolated infantile nystagmus to oculocutaneous albinism.

Expanding the Spectrum of FAT1 Nephropathies by Novel Mutations That Affect Hippo Signaling.

INTRODUCTION: Disease-causing mutations in the protocadherin FAT1 have been recently described both in patients with a glomerulotubular nephropathy and in patients with a syndromic nephropathy. METHODS: We identified 4 patients with FAT1-associated disease, performed clinical and genetic characterization, and compared our findings to the previously published patients. Patient-derived primary urinary epithelial cells were analyzed by quantitative polymerase chain reaction (qPCR) and immunoblotting to identify possible alterations in Hippo signaling. RESULTS: Here we expand the spectrum of FAT1-associated disease with the identification of novel FAT1 mutations in 4 patients from 3 families (homozygous truncating variants in 3, compound heterozygous missense variants in 1 patient). All patients show an ophthalmologic phenotype together with heterogeneous renal phenotypes ranging from normal renal function to early-onset end-stage kidney failure. Molecular analysis of primary urine-derived urinary renal epithelial cells revealed alterations in the Hippo signaling cascade with a decreased phosphorylation of both the core kinase MST and the downstream effector YAP. Consistently, we found a transcriptional upregulation of bona fide YAP target genes. CONCLUSION: A comprehensive review of the here identified patients and those previously published indicates a highly diverse phenotype in patients with missense mutations but a more uniform and better recognizable phenotype in the patients with truncating mutations. Altered Hippo signaling and de-repressed YAP activity might be novel contributing factors to the pathomechanism in FAT1-associated renal disease.

Tendon elongation with bovine pericardium in strabismus surgery-indications beyond Graves' orbitopathy.

BACKGROUND: For some patients with complex ocular motility disorders, conventional strabismus surgery is insufficient. Surgery with tendon elongation allows correction of larger angles and maintains a sufficient arc of contact for rectus muscles. This study reports results for tendon elongation with bovine pericardium (Tutopatch®) in indications other than Graves' orbitopathy in which it is already widely used. METHODS: We reviewed the records of all patients who underwent surgery with Tutopatch® in our institution. Angles of squint and head postures were analyzed preoperatively, on the first postoperative day, and in the long term (median 9 weeks after the operation). Patients with Graves' orbitopathy were excluded. RESULTS: From 2011 to 2018, the procedures on 58 eyes of 54 patients (35 females, median age 35 years (3-75)) met the inclusion criteria. Horizontal rectus muscle surgery (53 eyes) was conducted on patients with residual strabismus (13), Duane's retraction syndrome with eso- (type I: 16)/exodeviation (type II: 2, type III: 1), 6th (7)/3rd nerve palsy (7), Möbius syndrome (2), congenital fibrosis of the extraocular muscles type 3A (CFEOM3A, TUBB3 mutation) (4), and orbital apex syndrome (1). Vertical rectus muscle surgery (5 eyes) was conducted on patients with myasthenia (1), vertical tropia after orbital floor fracture (1), CFEOM1 (2), and Parry-Romberg syndrome (1). 42 eyes had prior eye muscle surgery (1-5 procedures, median 1). Out of 45 patients with postoperative long-term data, 43 showed an angle reduction. Fifty-one percent had an angle of 10Δ (prism diopter) or less, one had a significant over-effect, and 10 had revision surgery. For the heterogeneous group of residual eso- and exotropias, the median absolute horizontal angle was reduced from 35Δ (16 to 45Δ) to 9Δ (0 to 40Δ), for Duane's retraction syndrome from 27.5Δ (9 to 40Δ) to 7Δ (0 to 40Δ), and for sixth and third nerve palsies from 43Δ (20 to 75Δ) to 18Δ (4 to 40Δ). For 3 patients with vertical rectus muscle surgery, the median absolute vertical angle was reduced from 30Δ (20 to 45Δ) to 4Δ (1 to 22Δ). The motility range was shifted in the direction contrary to the elongated muscle in all subgroups. A considerable reduction of the excursion into the field of action of the elongated muscle had to be registered. CONCLUSIONS: Strabismus surgery with bovine pericardium introduces new surgical options for complicated revisions and for rare and complex oculomotor dysfunctions. Yet, it has to be recognized that this type of surgery aiming at maximum effects, despite preservation or restitution of the arc of contact, leads to reduction of the excursion into the field of action of the elongated muscle. Furthermore, dose finding can be difficult depending on the underlying pathology and more than one intervention might be necessary for optimal results.

3D Versus 4K Display System - Influence of "State-of-the-art"-Display Technique on Surgical Performance (IDOSP-study) in Minimally Invasive Surgery: A Randomized Cross-over Trial.

OBJECTIVE: To evaluate if "state-of-the-art" 3D- versus 4K-display techniques could influence surgical performance. BACKGROUND: High quality minimally invasive surgery is challenging. Therefore excellent vision is crucial. 3D display technique (3D) and 2D-4K technique (4K) are designed to facilitate surgical performance, either due to spatial resolution (3D) or due to very high resolution (4K). METHODS: In randomized cross-over trial the surgical performance of medical students (MS), non-board certified surgeons (NBC), and board certified surgeons (BC) was compared using 3D versus 4K display technique at a minimally invasive training Parkour. RESULTS: One hundred twenty-eight participants were included (February 2018 through October 2019, 49 MS, 39 NBC, 40 BC). The overall Parkour time (s) 3D versus 4K was 712.5 s ± 17.5 s versus 999.5 s ±â€Š25.1 s (P < 0.001) for all levels of experience. It was (3D vs 4K) for MS (30 tasks) 555.4 s ±â€Š28.9 s versus 858.7 s ±â€Š41.6 s, (P < 0.0001), for NBC (42 tasks) 935.9 s ±â€Š31.5 s versus 1274.1 s ±â€Š45.1 s (P =< 0.001) and for BC (42 task) 646.3 s ±â€Š30.9 s versus 865.7 s ±â€Š43.7 s (P < 0.001). The overall number of mistakes was (3D vs 4K) 10.0 ±â€Š0.5 versus 13.3 ±â€Š0.7 (P < 0.001), for MS 8.9 ±â€Š0.9 versus 13.1 ±â€Š1.1 (P < 0.001), for NBC 12.45 ±â€Š1.0 versus 16.7 ±â€Š1.2 (P < 0.001) and for BC 8.8 ±â€Š1.0 versus 10.0 ±â€Š1.2 (P = 0.18). MS, BC, and NBC showed shorter performance time in 100% of the task with 3D (significantly in 6/7 tasks). For number of mistakes the effect was less pronounced for more experienced surgeons. The National Aeronautics and Space Administration-task load index was lower with 3D. CONCLUSION: 3D laparoscopic display technique optimizes surgical performance compared to the 4K technique. Surgeons benefit from the improved visualization regardless of their individual surgical expertise.

Differential Diagnosis of Acquired Esotropia in the Elderly. / Differenzialdiagnose der erworbenen Esotropie im Alter.

AIM: To provide an overview of the differential diagnoses of acquired esotropia that occur in the elderly and to facilitate their differentiation in everyday clinical practice. METHODS: The data of all patients who presented in our outpatient university department for strabology and neuroophthalmology from March 2014 to October 2015 due to esotropia with diplopia with onset after age 50 were evaluated retrospectively. Exclusion criteria were a known strabismus before the age of 50 and/or vertical deviations in the primary position. Anamnestic characteristics, accompanying findings and orthoptic parameters, were analysed. RESULTS: 85 patients were included in the study, 42 of them female and 43 male. The following diagnoses were made: abducens nerve palsy (n = 34, 3 of them both sides), esotropia due to myopia magna (n = 12), esotropia with accompanying neurological symptoms (n = 6) and other etiology (n = 5). In 4 cases, the diagnosis was still unclear at the end of the study. In 24 patients, none of the above diagnoses existed and the diagnosis of "sagging eye syndrome" (ETSAG) was made. The abducens nerve palsy typically showed a sudden onset of double vision, slowed abduction saccades and asymmetrical abduction ability. With unilateral abducens nerve palsy, the esotropia increased continuously from the view to the unaffected side through the primary position to the view to the affected side. Patients with ETSAG and myopia-associated esotropia, on the other hand, reported a gradual onset of double vision, showed normal abduction saccades and a slightly reduced abduction ability. The squint angle often increased slightly to both sides. Esotropia with accompanying neurological symptoms was rare and was seen in various underlying diseases. CONCLUSIONS: The kind of onset of the double vision, the quality of the saccades, the incomitance pattern and the ability to abduct are important parameters for the etiological assignment of an esotropia in the elderly. The characteristics of the individual diagnoses are described and differential diagnostic aspects are discussed.

Correction to: 3D vs. 4 K Display System - Influence of "State-of-the-art"-Display Technique On Surgical Performance (IDOSP-Study) in minimally invasive surgery: protocol for a randomized cross-over trial.

After publication of our article [1] the authors have notified us that one of the names has been incorrectly spelled.

3D vs. 4K Display System - Influence of "State-of-the-art"-Display Technique On Surgical Performance (IDOSP-Study) in minimally invasive surgery: protocol for a randomized cross-over trial.

BACKGROUND: Three-dimensional (3D) stereoscopic vision is crucial to perform any kind of manual task. The reduction from real life 3D to virtual two-dimensional (2D) sight is a major challenge in minimally invasive surgery (MIS). A 3D display technique has been shown to reduce operation time and mistakes and to improve the learning curve. Therefore, the use of a3D display technique seems to optimize surgical performance for novice and experienced surgeons. Inspired by consumer electronics, a 4K display technique was recently introduced to MIS. Due to its high resolution and zoom effect, surgeons should benefit from it. The aim of this study is to evaluate if "state-of-the-art" 3D- vs. 4K-display techniques could influence surgical performance. METHODS: A randomized, cross-over, single-institution, single-blinded trial is designed. It compares the primary outcome parameter "surgical performance", represented by "performance time "and "number of mistakes", using a passive polarizing 3D and a 4K display system (two arms) to perform different tasks in a minimally invasive/laparoscopic training parkour. Secondary outcome parameters are the mental stress load (National Aeronautics and Space Administration (NASA) Task Load Index) and the learning curve. Unexperienced novices (medical students), non-board-certified, and board-certified abdominal surgeons participate in the trial (i.e., level of experience, 3 strata). The parkour consists of seven tasks (for novices, five tasks), which will be repeated three times. The 1st run of the parkour will be performed with the randomized display system, the 2nd run with the other one. After each run, the mental stress load is measured. After completion of the parkour, all participants are evaluated by an ophthalmologist for visual acuity and stereoscopic vision with five tests. Assuming a correlation of 0.5 between measurements per subject, a sample size of 36 per stratum is required to detect a standardized effect of 0.5 (including an additional 5% for a non-parametric approach) with a power of 80% at a two-sided type I error of 5%. Thus, altogether 108 subjects need to be enrolled. DISCUSSION: Complex surgical procedures are performed in a minimally invasive/laparoscopic technique. This study should provide some evidence to decide which display technique a surgeon could choose to optimize his performance. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03445429 . Registered on 7 February 2018.

[Efficacy of Vertical Muscle Transpositions with and without Simultaneous Rectus Muscle Recession for Unilateral Sixth Nerve Palsy]. / Effekt von Muskeltranspositionen nach dem Hummelsheim-Prinzip mit und ohne zeitgleiche Rücklagerung des M. rectus internus.

BACKGROUND: We report results of a modified vertical muscle transposition procedure according to the Hummelsheim principle - with and without simultaneous rectus muscle recession - for unilateral sixth nerve palsy. We examine the influence of the duration of the palsy, preoperative angle of squint and preoperative abductive capacity on surgical results of the procedures. PATIENTS AND METHODS: Retrospective study of 29 consecutive patients with unilateral abducens nerve palsy who underwent surgery between 2001 and 2012. 21 patients had a modified vertical rectus muscle transposition according to the Hummelsheim principle (HUM); 8 patients had this operation combined with simultaneous medial rectus muscle recession (HUM+I). Surgery was performed at least 9 months after onset of the palsy (HUM: 9 to 98, median 19, mean 30 months; HUM+I: 12 to 65, median 25, mean 29 months). RESULTS: The median preoperative angle of squint (far distance) for the HUM group was 27.0° (20.0 to 45.0; mean 28.1°), and for the HUM+I group 30.5° (21.8 to 50.0; mean 33.4°). The median preoperative abductive capacity was for - 1,6 mm before midline (- 8.0 to + 1.2; mean - 1.8 mm) for the HUM group, and - 3.0 mm before midline (- 10.0 to - 1.0; mean - 4.1 mm) for the HUM+I group. The median postoperative angle of squint (far distance) was 0° (- 11.3 to + 20.0; mean 0.1°) for the HUM group, and - 2.3° (- 11.3 to + 12.0; mean - 2.1°) for the HUM+I group. The median postoperative abductive capacity was 1.0 mm (0 to + 3.0; mean + 1.1 mm) for the HUM group, and 1.1 mm (- 1.2 to + 3.0; mean + 0.9 mm) for the HUM+I group. The median reduction of squint angle was 27.0° (9.1 to 45.0; mean 28.0°) for the HUM group, and 36.8° (25.2 to 41.4; mean 35.5°) for the HUM+I group. The median effect on abductive capacity was 2.5 mm (0 to 11.0; mean + 2.9 mm) for the HUM group, and 4.6 mm (2.4 to 8.8; mean + 5.0 mm) for the HUM+I group. In the HUM group, the effect on squint angle reduced with the duration of the palsy, whereas, in the HUM+I group, the effect improved with the duration of the palsy. CONCLUSIONS: For patients with unilateral sixth nerve palsy, simultaneous medial rectus recession increases the effect of modified vertical rectus muscle surgery according to the Hummelsheim principle. The duration of the palsy is a relevant parameter for the selection of a sole or combined intervention with medial rectus recession.

Mutation of POC1B in a severe syndromic retinal ciliopathy.

We describe a consanguineous Iraqi family with Leber congenital amaurosis (LCA), Joubert syndrome (JBTS), and polycystic kidney disease (PKD). Targeted next-generation sequencing for excluding mutations in known LCA and JBTS genes, homozygosity mapping, and whole-exome sequencing identified a homozygous missense variant, c.317G>C (p.Arg106Pro), in POC1B, a gene essential for ciliogenesis, basal body, and centrosome integrity. In silico modeling suggested a requirement of p.Arg106 for the formation of the third WD40 repeat and a protein interaction interface. In human and mouse retina, POC1B localized to the basal body and centriole adjacent to the connecting cilium of photoreceptors and in synapses of the outer plexiform layer. Knockdown of Poc1b in zebrafish caused cystic kidneys and retinal degeneration with shortened and reduced photoreceptor connecting cilia, compatible with the human syndromic ciliopathy. A recent study describes homozygosity for p.Arg106ProPOC1B in a family with nonsyndromic cone-rod dystrophy. The phenotype associated with homozygous p.Arg106ProPOC1B may thus be highly variable, analogous to homozygous p.Leu710Ser in WDR19 causing either isolated retinitis pigmentosa or Jeune syndrome. Our study indicates that POC1B is required for retinal integrity, and we propose POC1B mutations as a probable cause for JBTS with severe PKD.