Tethered vagina syndrome: massive urine loss caused by bladder neck scarring cured by skin graft.

The bladder neck area of the vagina is known as the "zone of critical elasticity" (ZCE). Adequate vaginal elasticity at ZCE is required for the oppositely-acting muscles to independently close the distal urethra and bladder neck. Scarring at ZCE "tethers" the more powerful posterior muscles to the anterior muscles and the bladder neck is forcibly pulled open, resulting in massive urine loss. This condition is known as "tethered vagina syndrome" (TVS). In developed countries, the main cause of TVS is iatrogenic. Vaginal repairs, vaginal mesh, may cause scarring at ZCE and this directly links the oppositely-acting muscle forces. Over-elevated Burch colposuspensions may stretch the ZCE to the point where its elasticity is lost so the muscles can no longer function independently. The treatment is to dissect the vagina clear of the scarring and to insert a skin graft to the bladder neck to restore ZCE elasticity. In developing countries, extensive trauma to the vagina and bladder from obstructed childbirth can cause obstetric fistulas. In up to 40-50% of these women, there is ongoing massive urine loss after the fistula has been successfully closed. Performing a prophylactical skin graft during fistula closure if there is vaginal tissue deficit is proving to be revolutionary. In women with Goh type 4 fistula (n=45), 46% were cured (full dryness) against an expected 19%. The same operation can produce equally dramatic cures in women who continue to leak urine after successful fistula repair.

Peripheral muscle force balance/imbalance in neurological binary control of bladder function and dysfunction.

Bladder control is not from the bladder itself but from muscles and ligaments outside of it. Bladder control is binary, either closed or open. Control is exerted cortically, directly and via a peripheral pelvic mechanism comprising three reflex pelvic muscles which contract (variously) against pubourethral ligaments (PULs) anteriorly and uterosacral ligaments (USLs) posteriorly. Directed efferent impulses from the cortex close the urethra, open it, and stretch the vagina in opposite directions to prevent urothelial impulses inappropriately activating micturition (urge incontinence). Normally, the opposite muscles are equivalent in force, and balance at the bladder neck. Weak PULs weaken the forward closure force: the posterior forces become relatively more powerful; balance shifts behind bladder neck; the posterior urethral wall is pulled open like a trapdoor, and urine is lost on effort (stress urinary incontinence). Weak USLs weaken the posterior muscle forces; the balance of forces shifts forwards, and the urethra is closed relatively more tightly by slow-twitch forward muscle vector forces (pubococcygei), which stretch each side of the distal vagina forwards to compress the posterior urethral wall; in consequence, the weakened posterior muscle forces cannot easily open the posterior urethral wall; the bladder has to contract against a relatively unopened urethra, perceived as "obstructed micturition". Nor can weakened posterior forces stretch the vagina sufficiently to support the urothelial stretch receptors from below; these may fire off excess afferent impulses to cause urgency. As bladder control is strictly binary, in women with urgency, control swings between open and closed modes. This condition is known as an "unstable bladder", which is defined symptomatically as "overactive bladder", and urodynamically as "detrusor overactivity". In summary, bladder control is binary, either closed or open. How the cortex integrates and computes multiple inputs determines the type of closure, opening or unstable control which is experienced by the patient.

Diverse retinal-kidney phenotypes associated with NPHP1 homozygous whole-gene deletions in patients with kidney failure.

A precise diagnosis in medicine allows appropriate disease-specific management. Kidney failure of unknown aetiology remains a frequent diagnostic label within the haemodialysis unit and kidney transplant clinic, accounting for 15-20% of these patients. Approximately 10% of such cases may have an underlying monogenic cause of kidney failure. Modern genetic approaches can provide a precise diagnosis for patients and their families. A search for extra-renal disease manifestations is also important as this may point to a specific genetic diagnosis. Here, we present two patients where molecular genetic testing was performed because of kidney failure of unknown aetiology and associated retinal phenotypes. The first patient reached kidney failure at 16 years of age but only presented with a retinal phenotype at 59 years of age and was found to have evidence of rod-cone dystrophy. The second patient presented with childhood kidney failure at the age of 15 years and developed visual difficulties and photophobia at the age of 32 years and was diagnosed with cone dystrophy. In both cases, genetic tests were performed which revealed a homozygous whole-gene deletion of NPHP1-encoding nephrocystin-1, providing the unifying diagnosis of Senior-Løken syndrome type 1. We conclude that reviewing kidney and extra-renal phenotypes together with targeted genetic testing was informative in these cases of kidney failure of unknown aetiology and associated retinal phenotypes. The involvement of an interdisciplinary team is advisable when managing such patients and allows referral to other relevant specialities. The long time lag and lack of diagnostic clarity and clinical evaluation in our cases should encourage genetic investigations for every young patient with unexplained kidney failure. For these and similar patients, a more timely genetic diagnosis would allow for improved management, a risk assessment of kidney disease in relatives, and the earlier identification of extra-renal disease manifestations. Supplementary Information: The online version contains supplementary material available at 10.1007/s44162-024-00031-4.

Long term follow up of patients with MNV3 treated with intra-vitreal Aflibercept.

PURPOSE: MNV3 or Retinal angiomatous proliferation is a subtype of neovascular age-related macular degeneration (nAMD). We present the 5 year long term visual and anatomical outcomes of patients with MNV3 lesions treated with intravitreal Aflibercept. METHODS: This is a prospective study of treatment naïve patients with reading centre graded MNV3 lesions. After the loading phase, the patients received intravitreal Aflibercept as per the View study up to year 3, thereafter it was given on a prn basis. At each visit, best corrected visual acuity (BCVA) and optical coherence tomography (OCT) central macular thickness (CMT) was measured. RESULTS: Thirty one patients reached study completion. Mean BCVA of treated eyes had decreased by 0.6 ETDRS letters at the end of year 5 compared with baseline. At study completion, 81% of eyes had stable vision while 19% of eyes had gained 15 letters or more. At study end, 26% of eyes had BCVA of 6/12 or better, while 19% had lost 15 letters or more (all had central foveal photoreceptor loss). There was a maximal mean reduction in CMT of 164 microns (p = <0.0001) while 68% of maculae were fluid free at study completion. Eighty seven percent of treated eyes developed nascent GA, of which in 74% of eyes was involving the fovea. DISCUSSION: Despite initial improvement in mean BCVA, the improvement in BCVA was not maintained despite good overall control of the MNV3 lesions. The loss of BCVA was most likely due to the majority of eyes developing centre involving macular atrophy.

Treatment Strategy With Gene Editing for Late-Onset Retinal Degeneration Caused by a Founder Variant in C1QTNF5.

Purpose: Genome editing is an emerging group of technologies with the potential to ameliorate dominant, monogenic human diseases such as late-onset retinal degeneration (L-ORD). The goal of this study was to identify disease stages and retinal locations optimal for evaluating the efficacy of a future genome editing trial. Methods: Twenty five L-ORD patients (age range, 33-77 years; median age, 59 years) harboring the founder variant S163R in C1QTNF5 were enrolled from three centers in the United Kingdom and United States. Patients were examined with widefield optical coherence tomography (OCT) and chromatic perimetry under dark-adapted and light-adapted conditions to derive phenomaps of retinal disease. Results were analyzed with a model of a shared natural history of a single delayed exponential across all subjects and all retinal locations. Results: Critical age for the initiation of photoreceptor loss ranged from 48 years at the temporal paramacular retina to 74 years at the inferior midperipheral retina. Subretinal deposits (sRET-Ds) became more prevalent as critical age was approached. Subretinal pigment epithelial deposits (sRPE-Ds) were detectable in the youngest patients showing no other structural or functional abnormalities at the retina. The sRPE-D thickness continuously increased, reaching 25 µm in the extrafoveal retina and 19 µm in the fovea at critical age. Loss of light sensitivity preceded shortening of outer segments and loss of photoreceptors by more than a decade. Conclusions: Retinal regions providing an ideal treatment window exist across all severity stages of L-ORD.

MICROPERIMETRY IN FOVEAL-SPARING ATROPHIC LATE-ONSET RETINAL DEGENERATION.

PURPOSE: To understand the baseline and longitudinal microperimetry characteristics in foveal-sparing atrophic late-onset retinal degeneration. METHOD: Prospective, cross-sectional, longitudinal study in which patients from the retina clinics of two academic teaching hospitals were included. Mesopic microperimetry was performed using a Nidek MP-1 micro-perimeter. Mean total, foveal, inner ring, and outer ring sensitivities were analyzed. RESULTS: A total of 20 eyes from 10 patients had baseline data. The subset of 10 eyes from five patients had follow-up data. The mean baseline macular sensitivity was 10.02 dB (± 5.26) with findings showing symmetry between both eyes. In the follow-up cohort, there was a significant loss of outer ring (0.83 dB per year; P = 0.0001), inner ring (0.67 dB per year; P = 0.034), and foveal sensitivity (0.92 dB loss per year; P = 0.015), whereas the mean sensitivity decreased significantly (0.66 dB per year; P = 0.0008) at 4-year follow-up. The drop in mean sensitivity was associated with significant increases in the number of deep scotoma points (6.20, P = 0.037) and a decrease in the number of normal points (-6.30, P = 0.022). CONCLUSION: Microperimetry is a useful tool for macular function follow-up to measure disease progression in late-onset retinal degeneration.

Multiple Evanescent White Dot Syndrome and Choroidal Neovascularization following SARS-COV-2 Infection in a Patient on Dabrafenib and Trametinib.

PURPOSE: to describe multimodal imaging and electrophysiology of multiple evanescent white dot syndrome (MEWDS) concomitant with COVID-19 infection in a patient on BRAF (B Rapidly Accelerated Fibrosarcoma) and MEK (Mitogen-activated Protein Kinase) inhibitors. METHODS: observational case report and literature review. RESULTS: a 37-year-old woman affected by cutaneous melanoma on BRAF and MEK inhibitors developed visual symptoms in the right eye simultaneously with a SARS-COV-2 infection. The right eye visual acuity was hand movement, and clinical examination disclosed vitreous cells, yellow-white retinal spots, and macular yellowish material. Fundus autofluorescence and angiograms were consistent with MEWDS. Angiograms, optical coherence tomography, and optical coherence tomography angiography revealed a macular choroidal neovascular membrane. The infectious and inflammatory work-up was negative. Electrodiagnostic tests revealed cone dysfunction. MEWDS resolved and anti-VEGF treatment allowed partial vision recovery. CONCLUSION: the case illustrates the association of MEWDS and choroidal neovascularization developing after COVID-19 infection in the setting of immunotherapy.

THE PROGRESSION OF MACULAR STRUCTURAL AND FUNCTIONAL CHANGES IN LATE-ONSET RETINAL DEGENERATION.

BACKGROUND/PURPOSE: To characterize the progression of structural and functional changes in the retinas of a small cohort of unrelated patients with early late-onset retinal degeneration and evaluate these changes as potential biomarkers for future treatment trials. METHODS: Best-corrected visual acuity, contrast sensitivity, Goldman visual fields, retinal sensitivity measurement by mesopic microperimetry, extent of ellipsoid zone disruption using spectral domain optical coherence tomography, and fundus autofluorescence imaging were performed at each biennial visit. PATIENTS: Three unrelated patients with molecularly confirmed late-onset retinal degeneration (S163R mutation in C1QTNF5 ) were prospectively followed for 4 years. RESULTS: The patient's ages were 44, 54, and 62 at baseline. Over the 4-year follow-up period, one patient demonstrated a significant reduction in best-corrected visual acuity (6 Early Treatment of Diabetic Retinopathy Study letters), whereas two patients suffered a significant reduction in contrast sensitivity. Early in the disease, there was a close relationship between ellipsoid zone disruption and a loss in retinal sensitivity. Later in the course of the disease, there were areas outside the zones of ellipsoid zone disruption that also suffered progressive loss of retinal sensitivity, suggesting that ellipsoid zone loss was not the only factor responsible for the loss of retinal sensitivity. Changes in fundus autofluorescence and Goldman visual field loss were not closely related to changes in ellipsoid zone disruption or retinal sensitivity loss. CONCLUSION: This study has found that the monitoring of the progression of ellipsoid zone disruption and changes in mesopic microperimetry may be useful biomarkers in future clinical trials in patients with late-onset retinal degeneration.

Surgical repair and follow-up of chronic 4th degree obstetric perineal tear (total perineal defect) in 2 centres in eastern Africa.

INTRODUCTION AND HYPOTHESIS: Fourth-degree perineal tear occurs in up to 0.2% of vaginal deliveries. In limited resource communities, women often deliver in local villages without facilities to repair obstetric anal sphincter injuries. These fourth-degree tears heal by secondary intention and result in total perineal defects. The aim of the study is to present medium-term follow-up of a large number of women following repair of chronic fourth-degree tear. METHODS: Repairs of chronic obstetric fourth-degree tears were undertaken during surgical camps at Kagando Hospital, Uganda and Selian Hospital, Tanzania, from December 2013 to October 2019. Women completed Cleveland Clinic Incontinence Scores (CCIS) on admission (face to face) and during the 7-year follow-up period (via telephone). RESULTS: Two hundred fourteen women had medical history and CCIS completed on admission. The mean age at presentation was 33.9 years and mean duration of the condition was 8.9 years. Over a third of women stated they suffered social abandonment because of the unrepaired fourth-degree tear. Nearly 45% of women suffered the tear during the first vaginal delivery. At 1-year follow-up, 87% of 101 women scored 0 (perfect continence) and 94% of 66 women had perfect continence at 2 years. Forty-one births occurred during the follow-up period (32 vaginal deliveries) with two recurrences of fourth-degree tear. CONCLUSIONS: Follow-up in limited resource communities is challenging. Short- to medium-term results of women who had repair of total perineal defect (unrepaired fourth-degree obstetric tears) are encouraging.

Long-term follow-up of a patient with JAG1-associated retinopathy.

PURPOSE: To report the long-term structural and functional changes in the posterior segments of an adult with an unusual retinal dystrophy caused by a novel mutation in JAG1. METHODS: A 33-year-old female underwent comprehensive ophthalmic examination, including best corrected visual acuity (BCVA) measurement, dilated fundus imaging (wide-angle fundus colour and short wavelength autofluorescence imaging), macular and peripheral spectral-domain optical coherence tomography (SD-OCT) and electroretinography (ERG) at baseline and 10 years later at the age of 43. The patient also underwent systemic review with detailed cardiac, brain and renal investigations. During follow-up, genetic analysis using whole-exome sequencing was performed on the patient and her parents to identify disease-causing variants. RESULTS: The patient's main complaint was of a recent onset of bilateral photophobia and blurred vision in the left eye. On examination, the most striking retinal finding was of bilateral well-demarcated, anterior circumferential chorioretinal atrophy with scattered pigment clumping from the mid periphery to the ora. In addition, she had posterior pole RPE hypopigmentation, peripapillary chorioretinal atrophy, left macular choroidal folds and retinal vasculature tortuosity with atypical branching. Her retinal electrophysiology was consistent with a cone rod photoreceptor dystrophy and left macular dysfunction. Ten years later, her BCVA, the anterior circumferential chorioretinal atrophy and her visual field constriction all remained stable. Her retinal electrophysiology demonstrated deterioration of left rod function, while cone dysfunction remained stable. Macular function deteriorated in both eyes. During follow-up, she was also noted to have progressive aortic root dilatation, posterior embryotoxon and an x ray diagnosis of butterfly vertebrae. Whole-exome sequencing revealed a novel c.2412C > A p.(Tyr804Ter) truncating mutation in JAG1 that was predicted to be pathogenic and suggested a diagnosis of Alagille syndrome. CONCLUSION: This is the first report of the long-term detailed follow-up of a patient with Alagille syndrome whose most striking ophthalmic finding was bilateral well-demarcated, anterior circumferential chorioretinal atrophy. During follow-up, this finding remained stable, suggesting that this may be developmental in origin. This is in contrast with the progressive deterioration in the posterior pole retinal and macular function.

Reticular Pseudodrusen in Late-Onset Retinal Degeneration.

PURPOSE: To characterize the association of reticular pseudodrusen (RPD) with late-onset retinal degeneration (L-ORD) using multimodal imaging. DESIGN: Prospective, 2-center, longitudinal case series. PARTICIPANTS: Twenty-nine patients with L-ORD. METHODS: All patients were evaluated within a 3-year interval with near-infrared reflectance, fundus autofluorescence, and spectral-domain OCT. In addition, a subset of patients also underwent indocyanine green angiography, fundus fluorescein angiography, mesopic microperimetry, and multifocal electroretinography. MAIN OUTCOME MEASURES: Prevalence, topographic distribution, and temporal phenotypic changes of RPD in L-ORD. RESULTS: A total of 29 patients with molecularly confirmed L-ORD were included in this prospective study. Reticular pseudodrusen was detected in 18 patients (62%) at baseline, 10 of whom were men. The prevalence of RPD varied with age. The mean age of RPD patients was 57.3 ± 7.2 years. Reticular pseudodrusen was not seen in patients younger than the fifth decade of life (n = 3 patients) or in the eighth decade of life (n = 5 patients). Reticular pseudodrusen were found commonly in the macula with relative sparing of the fovea and also were identified in the peripheral retina. The morphologic features of RPD changed with follow-up. Two patients (3 eyes) demonstrated RPD regression. CONCLUSIONS: Reticular pseudodrusen is found frequently in patients with L-ORD and at a younger age than in individuals with age-related macular degeneration (AMD). Reticular pseudodrusen exhibits quick formation and collapse, change in type and morphologic features with time, and relative foveal sparing and also has a peripheral retinal location in L-ORD.

Acute Macular Neuroretinopathy Associated with Acute Influenza Virus Infection.

Purpose: To describe a prospective case series of patients with acute macular neuroretinopathy (AMN) associated with acute influenza virus infectionMethods: Patients who presented with acute macular neuroretinopathy associated with confirmed influenza virus infection were subject to a detailed clinical history, HLA typing and longitudinal ophthalmological and imaging examinations.Results: Four female patients aged 18 to 32 years were studied. They reported the onset of ocular symptoms between 2 and 5 days after the development of flu like symptoms. Three patients had confirmed acute influenza B infection, while the fourth had influenza A. OCT angiography only demonstrated abnormal choriocapillaris perfusion in 1 patient and early oral Oseltamivir treatment appeared not to affect the ophthalmic outcome in one patient.Conclusion: This is the first report of AMN associated with virologically confirmed acute influenza virus infection. Variation in HLA alleles do not appear to predispose patients to influenza associated AMN.

Prophylactic Autologous Slings at the Time of Obstetric Fistula Repair: A Randomized Clinical Trial.

OBJECTIVE: To compare prophylactic slings for women with obstetric fistulas at high risk of residual incontinence. METHODS: This was a multiple-site randomized controlled trial comparing autologous fascia slings to pubococcygeal (PC) slings at time of fistula repair. Women with a Goh type 3 or 4 vesicovaginal fistula (distal edge of the fistula is ≤2.5 cm from the external urethral orifice) with no prior repair were randomized to receive either a rectus fascia sling or a PC sling while undergoing fistula repair. Interviews were performed before surgery and at follow-up 1 to 6 months later including the Michigan Incontinence Symptom Index and the Incontinence Quality of Life Tool. Pad weights were also collected at this time. Safety analysis was performed after 10 participants were enrolled in each arm. RESULTS: Eleven participants randomized to a PC sling and 10 to a rectus sling. There was 1 repair breakdown in the PC group and 3 in the rectus group. There was no significant difference noted in pad weights or quality of life scores between groups. Quality of life and Michigan Incontinence Symptom Index scores improved significantly for both groups after surgery. The study was terminated at safety analysis due to the number of breakdowns and difficulty of follow-up at 1 site. CONCLUSIONS: There was no superiority between slings. Randomization proved problematic given the vast heterogeneity between fistula injuries. There is a need for an innovative anti-incontinence technique.ClinicalTrials.gov identifier: NCT03236922 https://www.clinicaltrials.gov/ct2/show/NCT03236922?cond=vesico-vaginal+fistula&rank=2.

CHARACTERIZING THE NATURAL HISTORY OF FOVEAL-SPARING ATROPHIC LATE-ONSET RETINAL DEGENERATION.

PURPOSE: To identify quantifiable markers of disease progression in patients with foveal-sparing atrophic late-onset retinal degeneration using fundus autofluorescence and spectral-domain optical coherence tomography imaging. METHODS: Natural history study evaluating patients within a 3-year interval. Disease progression was assessed based on the area of retinal atrophy, macular topographic distribution of lesions, retinal and choroidal thickness and volume, and choroidal vascularity index. RESULTS: Twenty-four eyes (12 individuals) were included for fundus autofluorescence, and 31 eyes (16 individuals) for spectral-domain optical coherence tomography studies. Measurements were symmetrical between eyes of the same patient. The area of atrophy significantly enlarged (P = 0.002), with a growth rate of 2.67 mm2/year (SD: 2.13; square rooted: 0.57 mm/year, SD = 0.34). Baseline area of atrophy and progression both correlated with age. Most atrophic lesions were found in the temporal macula and progressed nasally at follow-up. Central choroidal and retinal thicknesses and volume in late-onset retinal degeneration cases were significantly reduced compared with controls, but only central retinal thickness decreased significantly at follow-up. CONCLUSION: This study identifies the area of atrophy and central retinal thickness, but not chorioretinal volume or choroidal thickness, as markers of short-term progression in late-onset retinal degeneration. These findings may be useful for disease monitoring and late-onset retinal degeneration interventional studies.

Challenges in the field of obstetric fistula.

Thirteen years after the last supplement on obstetric fistula, the authors challenge the progress achieved. Citing the ongoing need for a standardized classification system, uniform surgical training and certification, evaluation, follow-up, and research, we emphasize the need for improved communication and coordination between government and nongovernment entities invested in ending obstetric fistula. Struck by the call by the United Nations to end obstetric fistula by 2030, we stress the need for increased and targeted funding of programs that are of the highest quality and impact.

Intravitreal Aflibercept for Retinal Angiomatous Proliferation: Results of a Prospective Case Series at 96 Weeks.

INTRODUCTION: Retinal angiomatous proliferation (RAP) is a subtype of neovascular age-related macular degeneration (nAMD). Untreated, the lesions are thought to be aggressive and lead to a poor visual outcome. Despite some limitations, studies reporting the treatment of RAP lesions with the intravitreal anti-VEGF drugs ranibizumab and bevacizumab have demonstrated variable but generally favourable responses. More recently, aflibercept has been licensed for the treatment of nAMD and may offer some advantages over other agents. We present the visual and anatomical outcomes at 96 weeks of patients with RAP lesions who were treated with intravitreal aflibercept, according to the pivotal VIEW study nAMD treatment protocol. METHODS: This is a prospective study of treatment-naïve patients with Reading Centre-graded RAP lesions. The patients received aflibercept every 8 weeks, after 3 initial monthly injections, up to and including week 48. During weeks 52-96, patients received injections at least every 12 weeks, with monthly evaluations for interim injections if they fulfilled the retreatment criteria. At each visit, best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) central macular thickness (CMT) were measured. RESULTS: Forty-six patients reached study completion at week 96. Mean BCVA had improved by 6.0 (standard deviation [SD] 7.9) and 4.8 (SD 7.4) ETDRS letters at 52 (p = 0.003) and 96 (p = 0.02) weeks, respectively, from a baseline of 57.3 (SD 12.0) letters. At 52- and 96-week time points, 45/46 (98%) and 41/46 (89%) of patients, respectively, had maintained their vision (<15 letters of BCVA lost). At the 96-week time point, 13/46 (28%) of patients had gained ≥15 letters and also demonstrated a mean reduction in CMT of 162 µm (SD 106) (p = <0.0001), with 72% of maculae being fluid-free. Using univariate analysis, we found no significant difference between any of the visual outcome measures in this study and the pivotal VIEW study; the mean number of injections required and change in CMT were also similar. CONCLUSIONS: In this study, we present the 96-week results, of the largest series to date, of patients treated prospectively with aflibercept for RAP using the VIEW protocol. We show that they benefited from treatment to a degree similar to those with type 1 and 2 nAMD.

A case of ocular cystinosis associated with two potentially severe CTNS mutations.

BACKGROUND: Ocular cystinosis is a rare autosomal recessive disorder caused by one severe and one mild mutation in the CTNS gene. It is characterised by cystine deposition within the cornea and conjunctiva however, the kidneys are not affected. We report a case of ocular cystinosis caused by two potentially severe CTNS mutations and discuss the possible mechanism of renal sparing. METHODS: This is an observational case report of the proband and her unaffected relatives. All subjects underwent ophthalmic examination, whilst in the proband, In vivo laser scanning confocal microscopy was used to demonstrate cystine crystals within her corneas and conjunctiva. Genetic diagnosis was confirmed by DNA sequencing of the proband and the segregation of the mutations was established in her relatives. RT-PCR of leukocyte RNA was undertaken to determine if aberrant splicing of the CTNS gene was taking place Results: The proband was found to have cystine crystals limited to the anterior corneal stroma and the conjunctiva. Sequencing of the proband's CTNS gene found her to be a compound heterozygote for a 27bp deletion in exon8/intron 8 (c.559_561 + 24del) and a novel c.635C>T variant in exon 9 that is predicted be pathogenic and to result in the substitution of alanine with valine at amino acid position 212 (p.Ala212Val), which is within the 3rd transmembrane spanning domain of the CTNS protein. Examination of the proband's leukocyte RNA failed to demonstrate any aberrant CTNS gene splicing. CONCLUSION: We present a case of ocular cystinosis caused by two potentially severe CTNS gene mutations. The lack of renal involvement may be due to localised (ocular) aberrant CTNS RNA splicing.