Bio

Bio


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BIOGRAPHY

Stephen J. Smith, MD is a Vitreoretinal Surgeon and Clinical Instructor (Affiliated) in Ophthalmology at the Byers Eye Institute, Department of Ophthalmology, at the Stanford University School of Medicine. His goal is to put the needs of his patients first, and this commitment to patient-centered care dictates his approach to both his clinical and surgical care.

Dr. Smith received a Bachelor of Science degree in Molecular Biology and earned his MD - graduating with distinction - from the Mayo Clinic College of Medicine. He completed his internship at Columbia University College of Physicians and Surgeon’s Bassett Medical Center. Dr. Smith was an ophthalmology resident at University of Michigan’s Kellogg Eye Center, consistently rated among the top 10 ophthalmology programs in the country. At University of Michigan he received numerous awards, including the Aizman Award, which is given to the resident who achieved the most significant scholarly achievement during residency with highest distinction in clinical excellence. Following a 2-year adult and pediatric vitreoretinal surgery fellowship at Stanford University’s Byers Eye Institute, he joined the vitreoretinal faculty on a part-time basis.

Dr. Smith specializes in the management of adult vitreoretinal diseases including exudative and non-exudative macular degeneration, diabetic retinopathy, retinal vascular occlusions, central serous chorioretinopathy, myopic maculopathy and immunogammopathy maculopathy. Dr. Smith’s surgical interests include complex retinal detachment repair, macular hole surgery, and scleral sutured fixated intraocular lens surgery. Dr. Smith is actively involved in the development of tools and techniques to improve vitreoretinal surgical outcomes, particularly for complex secondary IOL cases.

Dr. Smith is actively involved in the clinical and surgical training of Stanford’s vitreoretinal fellows. In addition, he serves as a research mentor. His particular interest is in working with retina fellows and ophthalmology residents who have expressed a desire to learn more about medical device and pharmaceutical innovation in retina, and uses his unique experience as an entrepreneur, clinician, and scientist to teach residents and fellows about the process of medical innovation, including fundraising, intellectual property, regulatory approvals, and business administration.

Clinical Focus


  • Ophthalmology
  • VItreoretinal Disease and Surgery
  • Macular Degeneration
  • Diabetic Retinopathy
  • Immunogammopathy Maculopathy
  • Complex Retinal Detachment Repair
  • Macular Hole
  • Epiretinal Membrane
  • Pathologic Myopia

Honors & Awards


  • Heed Fellow, Heed Ophthalmic Foundation (2016-2017)
  • Aizman Award, University of Michigan (2016)
  • Innovation Cup – 1st Place Award, University of Michigan (2016)
  • Walter R. Parker Resident Teaching Award – 2nd Place, University of Michigan (2016)
  • Heed Ophthalmic Foundation Resident Retreat – Nominated and selected to attend, Heed Ophthalmic Foundation (2015)
  • Promising Technology Award, University of Michigan (2015)
  • The George Slocum Resident Research Award – 1st Place, University of Michigan (2015)
  • Walter R. Parker Resident Teaching Award – 3rd Place, University of Michigan (2015)
  • Young Investigator Award and Travel Grant, European Paediatric Ophthalmological Society (2013)
  • Mayo Medical School Class of 2012 representative for the LCME re-accreditation site visit, Mayo Clinic College of Medicine (2011)
  • Dean's Outstanding Achievement Scholarship, Mayo Clinic College of Medicine (2008-2012)
  • Graduated Magna Cum Laude with high honors in molecular biology, Grove City College (2006)
  • Inductee: Beta Beta Beta National Biological Honor Society, Beta Beta Beta National Biological Honor Society (2005)
  • Inductee: Pi Gamma Mu International Honor Society in Social Sciences, Pi Gamma Mu International Honor Society in Social Sciences (2005)
  • Deans List with Distinction, Grove City College (2003-2006)
  • President’s Honor Role, University of Miami (2002)

Education & Certifications


  • Fellowship:Stanford University Retina and Vitreous FellowshipCA
  • Board Certification: Ophthalmology, American Board of Ophthalmology (2018)
  • Residency:University of Michigan Ophthalmology Residency (2016) MI
  • Internship:Bassett Medical Center (2013) NY
  • Medical Education:Mayo Medical School (2012) MN

Research & Scholarship

Current Research and Scholarly Interests


RESEARCH OVERVIEW

Dr. Smith’s primary professional interest is developing solutions for unmet clinical and surgical vitreoretinal needs. Beginning in medical school, one of his primary focuses has been improving treatment outcomes in patients with retinoblastoma (RB). During his second year in medical school Dr. Smith published a manuscript on a novel technique to reduce the risk of tumor spread following intravitreal drug delivery in patients with RB. His work summarizing published data on tumor spread following intravitreal injection therapy (IVT) for RB has resulted in multiple platform presentations at national and international meetings, including an invited lecture at ARVO 2014. The results of this study influenced the growing trend toward broader acceptance of intravitreal chemotherapy in pediatric patients with treatment-resistant retinoblastoma vitreous seeds. A primary active area of research has included studying and publishing on ocular toxicity that results from the use of intravitreal melphalan and other agents for RB. This work, and subsequent publications from leaders in the field, has led to an increased awareness of ocular toxicity caused by injecting chemotherapeutic agents into the eyes of young children. This highlighted the need for toxicity data on additional chemotherapeutic agents for local delivery. To answer this question, Dr. Smith assembled an excellent group of collaborators and consultants, including internationally known experts at Bascom Palmer, Mayo Clinic, and Emory University. As a resident he secured a highly competitive career starter grant from the Knights Templar Foundation and used that funding and the expertise of his collaborators to carry out preclinical ocular toxicity studies of combination intravitreal chemotherapy for RB. His work in RB has led to a broader recognition of the challenges facing patients with RB who receive IVT and has led to a continued search for optimal local injectable therapies for patients with this disease.


INNOVATION HIGHLIGHTS

In addition to his work in retinoblastoma, Dr. Smith has been actively involved in developing technologies to improve outcomes for patients receiving intravitreal injection therapy (IVT) for macular degeneration, diabetic retinopathy, retinal vein occlusions and more. IVT has become the most common procedure performed by retina specialists in the United States, with an estimated 6 million injections given in the United States alone in 2016. Dr. Smith has co-developed technology that simplifies and streamlines the IVT process, removing barriers to treatment and improving patient outcomes. His work in innovation covers pre-clinical and clinical development work, and has given him expertise in diverse subject areas including fundraising, intellectual property portfolio development, team building, and business administration. He is a co-founder of iRenix Medical, a biotechnology and medical device start-up company committed to improving vision through optimization of the IVT process.

Dr. Smith remains dedicated to helping improve and restore vision and quality of life in patients with vitreoretinal disease. He is currently involved in both medical device and pharmaceutical innovation, and serves as a mentor for the Stanford University Biodesign Innovation Course.

Publications

All Publications


  • ENDOGENOUS KLEBSIELLA PNEUMONIAE ENDOPHTHALMITIS IN NORTHERN CALIFORNIA. Retina (Philadelphia, Pa.) Shields, R. A., Smith, S. J., Pan, C. K., Do, D. V. 2019; 39 (3): 614–20

    Abstract

    PURPOSE: To report the clinical features, treatment modalities, and visual outcomes in 12 eyes with endogenous Klebsiella pneumoniae endophthalmitis (EKPE).METHODS: The medical records of all patients diagnosed with EKPE at Stanford Hospital (Palo Alto, CA) and Santa Clara Valley County Hospital (Santa Clara, CA) from January 2000 to March 2017 were retrospectively reviewed.RESULTS: A total of 10 patients (12 eyes) were diagnosed with EKPE. The median age at presentation was 56, 80% were male, and 30% were non-Asian. Presenting visual acuities ranged from 20/20 to no light perception. Of the 12 eyes 10 received a tap and injection (range, 1-33 injections per eye), 2 eyes underwent primary enucleation or evisceration, and 1 patient underwent pars plana vitrectomy after tap and injection. Final visual acuities ranged from no light perception (six eyes) to 20/300 or better (five eyes). Five patients eventually underwent evisceration or enucleation. All cases were associated with positive blood and/or vitreous cultures and had concurrent systemic infection.CONCLUSION: Endogenous Klebsiella pneumoniae endophthalmitis is a rare, but devastating, ocular infection. Most cases in this series resulted in light perception vision or worse, and almost half required enucleation or evisceration. In light of the virulence of EKPE, early diagnosis and treatment should be initiated in all suspected cases.

    View details for PubMedID 29232335

  • Optical Coherence Tomography Angiography Highlights Chorioretinal Lesions in Ocular Coccidioidomycosis OPHTHALMIC SURGERY LASERS & IMAGING RETINA Shields, R. A., Tang, P. H., Bodnar, Z. M., Smith, S. J., Silva, A. 2019; 50 (3): E71–E73

    Abstract

    A 34-year-old woman presented after recovering from a disseminated Coccidioides immitis infection of the lungs, blood, brain, and placenta. The patient was asymptomatic for visual complaints. Visual acuity was 20/20 in both eyes. Fundus examination demonstrated bilateral chorioretinal infiltrates worse in the left eye. Fluorescein angiography (FA) was unable to be performed as the patient was breastfeeding, prompting the use of optical coherence tomography angiography (OCTA) imaging to further investigate the infiltrates. OCTA imaging was able to detect all visualized chorioretinal infiltrates and showed an additional non-visualized deep choroidal lesion. OCTA is a valuable tool in detecting chorioretinal lesions when FA is contraindicated. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e71-e73.].

    View details for DOI 10.3928/23258160-20190301-14

    View details for Web of Science ID 000462056800004

    View details for PubMedID 30893459

  • Postoperative Adverse Events, Interventions, and the Utility of Routine Follow-Up After 23-, 25-, and 27-Gauge Pars Plana Vitrectomy. Asia-Pacific journal of ophthalmology (Philadelphia, Pa.) Shields, R. A., Ludwig, C. A., Powers, M. A., Tran, E. M., Smith, S. J., Moshfeghi, D. M. 2019

    Abstract

    PURPOSE: To evaluate the utility of standard postoperative visit (POV) intervals in pars plana vitrectomy (PPV) as a function of adverse events (AEs) identified.DESIGN: Retrospective case review.METHODS: The medical records of all patients undergoing 23-, 25-, and 27-gauge PPV from January 1, 2016 to December 31, 2016 were reviewed. Each POV was assessed as a standard (s-POV), physicianadjusted (a-POV), or patient-initiated visit (p-POV). Preoperative features, diagnoses, and surgical procedures were evaluated to determine protective and risk factors for AEs.RESULTS: A total of 256 patients (310 PPVs) were included in this study. The most common cumulative postoperative AEs were elevated intraocular pressure (>30 mm Hg) (12.3%), cystoid macular edema (6.1%), and retinal detachment (5.8%). Patients with the diagnosis of macular hole or epiretinal membrane had the lowest relative risk of AEs [0.30; 95% confidence interval (CI), 0.12-0.75 and 0.36; 95% CI, 0.21-0.63, respectively]. There was no difference in time to AE among different vitrectomy gauge sizes (P = 0.733). Patients in a-POV and p-POV groups had a statistically significant higher incidence of AEs in the POV day 5-10 window (P = 0.004).CONCLUSIONS: The utility of standard POVs in detecting AEs is dependent on the indication for PPV. Specifically patients undergoing isolated macular surgery (epiretinal membrane peel or macular hole repair) had the lowest relative risk of postoperative AEs and may warrant a less-intensive follow-up regimen.

    View details for PubMedID 30628767

  • A fatal case of Susac syndrome: The importance of ophthalmic examination in confirming the diagnosis. American journal of ophthalmology case reports Shields, R. A., Kleinman, R. A., Smith, S. J., Sanislo, S. R., Nguyen, Q. D. 2018; 12: 18–20

    Abstract

    Purpose: To report a fatal case of Susac syndrome in a 24-year-old female.Observations: A 24-year-old female presented with progressive encephalopathy of unknown etiology. Her previous evaluation consisted of laboratory testing, imaging, and a brain biopsy to investigate for infectious and rheumatologic diseases. Several months after onset of symptoms, she underwent ophthalmic examination, which demonstrated bilateral branch retinal artery occlusions. Further review of her medical record revealed a recent history of hearing loss. Based on the retinal and systemic findings, the patient was diagnosed with Susac syndrome. The patient was started on intensive immunosuppression; however, she became more obtunded and succumbed several months after her diagnosis.Conclusions and importance: The timely and accurate diagnosis of Susac syndrome, which classically manifests as the triad of encephalopathy, vestibulocochlear abnormalities, and retinal arteriolar occlusions, may help to reduce the morbidity of invasive testing and to prevent fatality.

    View details for PubMedID 30112461

  • Preclinical safety study of ultra-rapid, non-pharmacologic anesthesia for intravitreal injections. Smith, S., Kim, G., Pipe, K. P., Besirli, C. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018
  • Clinical feasibility of ultra-rapid, non-pharmacologic anesthesia for intravitreal injection in patients receiving anti-VEGF treatment Besirli, C. G., Smith, S., Pipe, K., Kim, G., Zacks, D. N., Gardner, T. W., Shah, A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018
  • Automatic identification of referral-warranted diabetic retinopathy using deep learning on mobile phone images Leng, T., Greven, M., Smith, S., Ludwig, C., Chang, R., Gargeya, R. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018
  • Preclinical Acute Ocular Safety Study of Combined Intravitreal Carboplatin and Etoposide Phosphate for Retinoblastoma OPHTHALMIC SURGERY LASERS & IMAGING RETINA Mohney, B. G., Elner, V. M., Smith, A. B., Harbour, J. W., Smith, B. D., Musch, D. C., Smith, S. J. 2017; 48 (2): 151-159

    Abstract

    To describe the ocular toxicity of intravitreal carboplatin and etoposide phosphate (VP16P) in Dutch-Belted rabbits.Twenty-two adult male Dutch-Belted rabbits (Cohort 1) each received a single, bilateral intravitreal injection (0.05 mL). For Cohort 1, safety was assessed via electroretinograms (ERGs) and ocular examination. Of nine total groups in Cohort 1, the first five received the following single agents: Group 1: normal saline; Group 2: VP16P 75 µg; Group 3: VP16P 100 µg; Group 4: carboplatin 4 µg; and Group 5: carboplatin 8 µg. Groups 6 through 9 received the following combination of carboplatin/ VP16P, respectively: Group 6: 8 µg/75 µg, Group 7: 8 µg/50 µg, Group 8: 4 µg/50 µg, and Group 9: 2 µg/25 µg. Cohort 2 consisted of 15 Dutch-Belted rabbits in seven groups (Groups 10 through 16), each receiving a single, bilateral intravitreal injection. For Cohort 2, safety was assessed via histopathology.Groups 2 through 8 demonstrated a statistically significant decrease (relative to Group 1) in at least one ERG waveform amplitude obtained 4 weeks postinjection (P < .05). Group 9 (carbo 2 µg/VP16P 25 µg) did not manifest ERG toxicity. Fundoscopic toxicity consisted of slight-to-moderate attenuation of vessels in rabbits receiving doses above carbo 4 µg/VP16P 50 µg. Histopathologic retinal toxicity (Cohort 2) was dose-dependent, ranging from full-thickness atrophy in rabbits receiving the highest dose to normal in rabbits receiving carbo 2 µg/VP16P 25 µg.Combined carboplatin and VP16P may be compatible for intravitreal injection therapy, and a single dose of 2 µg/25 µg appears to be safe in a rabbit model. These agents may be a safer alternative to intravitreal melphalan (Alkeran; GlaxoSmithKline, Brentford, United Kingdom) for the treatment of vitreous seeds in retinoblastoma. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:151-159.].

    View details for DOI 10.3928/23258160-20170130-09

    View details for Web of Science ID 000397235600009

    View details for PubMedID 28195618

  • Ocular Toxicity of Intravitreal Melphalan for Retinoblastoma Smith, S. J., Smith, B. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2015
  • Maculopathy in Patients with Monoclonal Gammopathy of Undetermined Significance Smith, S. J., Johnson, M. W. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2014
  • Ocular side effects following intravitreal injection therapy for retinoblastoma: a systematic review BRITISH JOURNAL OF OPHTHALMOLOGY Smith, S. J., Smith, B. D., Mohney, B. G. 2014; 98 (3): 292–97

    Abstract

    To describe the ocular side effects in patients receiving intravitreal injection therapy (IViT) for retinoblastoma.PubMed (1946-present), Scopus (all years), Science Citation Index (1900-present) and Conference Proceedings Citation Index-Science (1990-present) electronic databases were searched to identify all published reports of therapeutic intravitreal injections for retinoblastoma in humans.Ten studies with original IViT ocular side effect data were included in this systematic review. In these combined reports, a total of 1287 intravitreal injections were given to 306 eyes of 295 patients, with a mean follow-up of 74.1 months. Two hundred sixty-one (88.5%) patients received comparatively standard melphalan IViT doses (8-30 mcg). Ocular side effects occurred in 38 patients (17 significant, 21 minor). The proportion of patients experiencing potentially significant ocular side effects following standard melphalan IViT regimens was 0.031 (8/261; 95% CI 0.013 to 0.06). The side effects of these eight included iris atrophy in three, two each with chorioretinal atrophy and vitreous haemorrhage and one with retinal detachment. Of the other nine patients with significant complications, five experienced sight-threatening complications following dramatic dose escalations (four with melphalan, one with thiotepa), three experienced complications that are commonly associated with concurrent therapies given to these patients and one had a retinal detachment. Of the 61 patients receiving IViT via safety-enhancing injection techniques, all six significant side effects were either attributed to the therapeutic dose or confounded by concurrent treatments.Significant ocular complications following IViT for retinoblastoma are uncommon, and this risk may be reduced further by the use of careful injection technique and standard dosing regimens. Care must be taken in the dosing of intravitreal treatments to avoid potentially irreversible vision loss.

    View details for DOI 10.1136/bjophthalmol-2013-303885

    View details for Web of Science ID 000333483900003

    View details for PubMedID 24187047

  • Quantifying Diplopia with a Questionnaire OPHTHALMOLOGY Holmes, J. M., Liebermann, L., Hatt, S. R., Smith, S. J., Leske, D. A. 2013; 120 (7): 1492–96

    Abstract

    To report a diplopia questionnaire (DQ) with a data-driven scoring algorithm.Cross-sectional study.To optimize questionnaire scoring, 147 adults with diplopic strabismus completed both the DQ and the Adult Strabismus-20 (AS-20) health-related quality-of-life (HRQOL) questionnaire. To assess test-retest reliability, 117 adults with diplopic strabismus. To assess responsiveness to surgery, 42 adults (46 surgeries).The 10-item AS-20 function subscale score (scored 0-100) was defined as the gold standard for severity. A range of weights was assigned to the responses and the gaze positions (from equal weighting to greater weighting of primary and reading). Combining all response option weights with all gaze position weights yielded 382848 scoring algorithms. We then calculated 382848 Spearman rank correlation coefficients comparing each algorithm with the AS-20 function subscale score.To optimize scoring, Spearman rank correlation coefficients (measuring agreement) between DQ scores and AS-20 function subscale scores. For test-retest reliability, 95% limits of agreement and intraclass correlation coefficient (ICC). For responsiveness, change in DQ score.For the 382 848 possible scoring algorithms, correlations with AS-20 function subscale score ranged from -0.64 (best correlated) to -0.55. The best-correlated algorithm had response option weights of 5 for rarely, 50 for sometimes, and 75 for often, and gaze position weights of 40 for straight ahead in the distance, 40 for reading, 1 for up, 8 for down, 4 for right, 4 for left, and 3 for other, totaling 100. There was excellent test-retest reliability with an ICC of 0.89 (95% confidence interval, 0.84-0.92), and 95% limits of agreement were 30.9 points. The DQ score was responsive to surgery with a mean change of 51 ± 34 (P<0.001).We have developed a data-driven scoring algorithm for the DQ, rating diplopia symptoms from 0 to 100. On the basis of correlations with HRQOL, straight-ahead and reading positions should be highly weighted. The DQ has excellent test-retest reliability and responsiveness, and may be useful in both clinical and research settings.

    View details for DOI 10.1016/j.ophtha.2012.12.032

    View details for Web of Science ID 000321108500046

    View details for PubMedID 23531348

    View details for PubMedCentralID PMC3895465

  • Evaluating the risk of extraocular tumour spread following intravitreal injection therapy for retinoblastoma: a systematic review. The British journal of ophthalmology Smith, S. J., Smith, B. D. 2013; 97 (10): 1231–36

    Abstract

    Intravitreal injection therapy (IViT) for retinoblastoma has shown promise in the treatment of vitreous seeds; however, the potential for tumour dissemination following intravitreal penetration has limited its use. This review evaluates the risk of extraocular tumour spread in patients receiving therapeutic intravitreal injections for retinoblastoma.PUBMED (1946-present), SCOPUS (all years), Science Citation Index (1900-present) and Conference Proceedings Citation Index--Science (1990-present) electronic databases were searched to identify all published reports of IViT for retinoblastoma in humans.14 studies with original IViT data were included in this review. A total of 1304 intravitreal injections were given in 315 eyes of 304 patients, with one report of extraocular tumour spread and one patient in whom intravitreal treatment could not be excluded as a contributor to metastatic disease. The proportion of subjects with extraocular tumour spread potentially due to IViT in these combined reports was 0.007 (95% CI 0.0008 to 0.0236), with a mean follow-up of 72.1 months. In a subset of 61 patients receiving IViT via safety enhancing injection techniques (347 injections, 19.6 months mean follow-up), there were no reports of tumour spread.Local and systemic tumour spread following IViT in cases of retinoblastoma is rare, and this risk is potentially reduced by the use of safety enhancing injection techniques. These results suggest that the risk of tumour spread should not preclude IViT use for carefully selected patients as part of multi-modal globe salvaging therapy.

    View details for DOI 10.1136/bjophthalmol-2013-303188

    View details for PubMedID 23740960

  • Stereoacuity Thresholds before and after Visual Acuity Testing OPHTHALMOLOGY Smith, S. J., Leske, D. A., Hatt, S. R., Holmes, J. M. 2012; 119 (1): 164–69

    Abstract

    To compare stereoacuity thresholds before and after visual acuity testing in patients with intermittent strabismus and in controls.Prospective cohort study.Eighty-eight patients (41 with intermittent strabismus and 47 controls) with measurable stereoacuity on their initial stereoacuity test were enrolled prospectively.Stereoacuity was measured before and immediately after visual acuity testing using the near Preschool Randot and Distance Randot stereotests. Stereoacuity was transformed to log units for analysis.Change in stereoacuity thresholds (log seconds of arc [arcsec]).There was no overall deterioration in distance stereoacuity or near stereoacuity thresholds in either the intermittent strabismus or control groups. The mean change for patients with intermittent strabismus was 0.02 log arcsec (95% confidence interval [CI], -0.02 to 0.06) for near stereoacuity and 0.04 log arcsec (95% CI, -0.01 to 0.09) for distance stereoacuity. Control patients demonstrated a mean change of 0.03 log arcsec (95% CI, -0.01 to 0.06) for near stereoacuity and 0.01 log arcsec (95% CI, -0.06 to 0.08) for distance stereoacuity. These mean changes correspond to less than approximately one eighth of an octave. For individual patients, deterioration in stereoacuity beyond previously reported test-retest variability (0.6 log arcsec or more) was not observed in patients with intermittent strabismus or controls using either test.Stereoacuity thresholds do not deteriorate after visual acuity testing, and therefore measurements of stereoacuity do not need to precede visual acuity measurement or other tests that involve short periods of dissociation.The author(s) have no proprietary or commercial interest in any materials discussed in this article.

    View details for DOI 10.1016/j.ophtha.2011.06.041

    View details for Web of Science ID 000298639500026

    View details for PubMedID 21924502

    View details for PubMedCentralID PMC3258515

  • A Novel Mutation of LAMB2 in a Multigenerational Mennonite Family Reveals a New Phenotypic Variant of Pierson Syndrome OPHTHALMOLOGY Mohney, B. G., Pulido, J. S., Lindor, N. M., Hogan, M. C., Consugar, M. B., Peters, J., Pankratz, V., Nasr, S. H., Smith, S. J., Gloor, J., Kubly, V., Spencer, D., Nielson, R., Puffenberger, E. G., Strauss, K. A., Morton, D., Eldahdah, L., Harris, P. C. 2011; 118 (6): 1137–44

    Abstract

    To describe a novel laminin β-2 (LAMB2) mutation associated with nephrotic syndrome and severe retinal disease without microcoria in a large, multigenerational family with Pierson syndrome.Retrospective chart review and prospective family examination.An extended consanguineous family of 52 members.The eyes, urine, and serum DNA were evaluated in all family members after discovering 2 patients, both younger than 10 years, with bilateral retinal detachments and concurrent renal dysfunction. Linkage analysis was performed in the 9 living affected individuals, 7 using the Illumina Human Hap370 Duo Bead Array (Illumina, San Diego, CA) and 2 using GeneChip 10K (Affymetrix, Santa Clara, CA) mapping arrays.The prevalence and severity of ocular and kidney involvement and genetic findings.Eleven affected family members were identified (9 living), all manifesting chronic kidney disease and bilateral chorioretinal pigmentary changes, with or without retinal detachments, but without microcoria or neurodevelopmental deficits, segregating in an autosomal recessive pattern. The causative gene was localized to a 9-Mb region on chromosome 3. Comprehensive gene sequencing revealed a novel LAMB2 variant (c.440A → G; His147R) that was homozygous in the 9 living, affected family members, observed at a frequency of 2.1% in the Old Order Mennonite population, and absent in 91 non-Mennonite controls. The mutation is located in a highly conserved site in the N-terminal domain VI of LAMB2.This study describes a novel mutation of LAMB2 and further expands the spectrum of eye and renal manifestations associated with defects in the laminin β-2 chain.The author(s) have no proprietary or commercial interest in any materials discussed in this article.

    View details for DOI 10.1016/j.ophtha.2010.10.009

    View details for Web of Science ID 000291152700020

    View details for PubMedID 21236492

    View details for PubMedCentralID PMC3223484

  • Urine catecholamine levels as diagnostic markers for neuroblastoma in a defined population: implications for ophthalmic practice EYE Smith, S. J., Diehl, N. N., Smith, B. D., Mohney, B. G. 2010; 24 (12): 1792–96

    Abstract

    although elevated urinary catecholamine levels have been reported in 90-95% of patients with neuroblastoma, more recent studies of pediatric Horner syndrome caused by an underling neuroblastoma have reported normal values at presentation. The purpose of this population-based study is to report the percentage of cases of neuroblastoma with elevated urinary catecholamine levels at presentation and to suggest a recommended work-up for cases of idiopathic pediatric Horner syndrome.the medical records of all pediatric (<19 years) residents of Olmsted County, Minnesota diagnosed with neuroblastoma from 1 January 1969 through 31 December 2008 were retrospectively reviewed.a total of 14 patients <19 years of age were diagnosed with neuroblastoma as residents of Olmsted County, Minnesota, during the 40-year study period. A total of 10 (71%) of the 14 cases manifested elevated urinary catecholamine metabolites at the initial presentation. Urinary vanillylmandelic acid (VMA) levels were greater than twice the upper limit of normal in eight (57%) of 14 cases, whereas homovanillic acid (HVA) levels were greater than two times the upper limit of normal in 10 (71%) of the 14 cases. Three (75%) of the four cases without significantly elevated urinary VMA or HVA levels were diagnosed with stage IV disease, whereas one (25%) had stage II neuroblastoma.urinary catecholamine levels were significantly elevated at presentation in 10 (71%) of the 14 neuroblastoma cases during the 40-year study period, suggesting that greater emphasis be placed on performing a thorough physical examination and obtaining warranted imaging studies in cases of idiopathic pediatric Horner syndrome.

    View details for DOI 10.1038/eye.2010.125

    View details for Web of Science ID 000285138500007

    View details for PubMedID 20865029

    View details for PubMedCentralID PMC3277743

  • Incidence, Ocular Manifestations, and Survival in Children with Neuroblastoma: A Population-Based Study AMERICAN JOURNAL OF OPHTHALMOLOGY Smith, S. J., Diehl, N. N., Smith, B. D., Mohney, B. G. 2010; 149 (4): 677–82

    Abstract

    To determine the incidence, ophthalmic manifestations, and survival among children with neuroblastoma in a defined population.Population-based retrospective cohort.The medical records of all pediatric (<19 years) residents of Olmsted County, Minnesota, diagnosed with neuroblastoma from January 1, 1969, through December 31, 2008, were retrospectively reviewed.Fourteen children were diagnosed with neuroblastoma as residents of Olmstead County, Minnesota, during the 40-year period, yielding an age- and gender-adjusted incidence of 11.8 (95% confidence interval [CI]: 5.6-18.0) per million patients <15 years of age. The calculated incidence for patients presenting before the age of 5 in this cohort was 1 in 5970 children (95% CI: 3920-12 580 children). The mean age at diagnosis for the 14 study patients was 22.5 months (range, 10.4-42.6 months). Six of the 14 (43%; 95% CI: 18%-71%) had ocular manifestations, including orbital metastasis in 6 (100%), proptosis and ecchymosis in 4 (67%), ptosis in 2 (33%), and strabismus in 1 (17%). The Kaplan-Meier rate of survival for all 14 children was 57% at 1 year (95% CI: 36%-90%) and 50% at 5 years (95% CI: 30%-84%), while the 6 with eye findings had a survival rate of 17% at 9 months (95% CI: 3%-100%).The incidence of neuroblastoma in this population was 11.8 per million patients <15 years, with ophthalmic involvement observed in 6 of the 14 study patients (43%). Orbital metastasis in the 6 children in this cohort was associated with poor prognosis.

    View details for DOI 10.1016/j.ajo.2009.11.027

    View details for Web of Science ID 000276575700021

    View details for PubMedID 20149339

    View details for PubMedCentralID PMC3905802

  • Incidence of Pediatric Horner Syndrome and the Risk of Neuroblastoma A Population-Based Study ARCHIVES OF OPHTHALMOLOGY Smith, S. J., Diehl, N., Leavitt, J. A., Mohney, B. G. 2010; 128 (3): 324–29

    Abstract

    To describe the incidence of pediatric Horner syndrome and the risk of occult malignancy in a population-based cohort.The medical records of all pediatric patients (aged <19 years) residing in Olmsted County, Minnesota, who received diagnoses of Horner syndrome from January 1, 1969, through December 31, 2008, were retrospectively reviewed.Horner syndrome was diagnosed in 20 pediatric patients during the 40-year period, yielding an age- and sex-adjusted incidence of 1.42 per 100 000 patients younger than 19 years of age (95% confidence interval [CI], 0.80-2.04). Eleven of the 20 patients (55%) had a congenital onset, for a birth prevalence of 1 in 6250 (95% CI, 3333-10 000), while the remaining 9 (45%) had acquired syndromes. Seven of the 11 (63.6%) patients with congenital cases had a history of birth trauma, while the remaining 4 (36.4%) had no identifiable cause. Six of the 9 (66%) acquired cases occurred following surgery or trauma, while the remaining 3 (33%) had no known etiology. None of the 20 patients (95% CI, 0.0%-16.8%) were found to have a neuroblastoma or other malignancy during a mean follow-up of 56.5 months (range, 0-256.9 months).The incidence of pediatric Horner syndrome in this population was 1.42 per 100 000 patients younger than 19 years, with a birth prevalence of 1 in 6250 for those with a congenital onset. Birth, surgical, or other trauma occurred in 13 (65%) of the patients, while none were found to have an underlying mass lesion, suggesting a need for reappraising current recommendations for extensive evaluations in these patients.

    View details for DOI 10.1001/archophthalmol.2010.6

    View details for Web of Science ID 000275308100008

    View details for PubMedID 20212203

    View details for PubMedCentralID PMC3743544