1p36 duplication syndrome: Advocacy for genetic testing and co-management for pediatric patients with systemic or ocular findings consistent with this rare chromosomal anomaly
Published 2021 by Mandip Chahil
Article Type: Residents Day
Abstract:
1p36 duplication syndrome is a rare, often significant, and potentially fatal chromosomal anomaly. Genetic testing and appropriate inter-disciplinary co-management are indicated to provide comprehensive care for children with various phenotypic manifestations of this syndrome.
Case History:
9 YO Male
Chief complaint:
Blurry distance vision
Ocular History:
Compound Myopic Astigmatism (CMA)
Medical history:
ADHD
Developmental/Intellectual delays
Seizures
Subaortic stenosis
Family history:
None
Medications:
Adderall
Clonazepam
Pertinent Findings:
Clinical:
Mild increase in myopia
Good BCVA OD/OS
Other findings WNL OU
Radiology studies:
MRI Brain: No encephalopathy
Echocardiogram: Mild subaortic stenosis
Electroencephalography: Childhood epilepsy
Genetic testing:
Chromosomal Microarray:
Pure 1p36 duplication
Involving genes of potential clinical significance including NADK, GNB1, CALML6, TMEM52, KIAA1751, GABRD, PRKCZ, C1orf86, SKI, MORN1, LOC100129534
Differential Diagnosis:
Genetic syndromes:
1p36 duplication syndrome
Fragile X syndrome
Cri-du-chat syndrome
Angelman syndrome
Non-syndromic concurrent cardiac, neurologic, psychologic findings and refractive error
Diagnosis & Discussion:
Genetic testing with chromosomal microarray confirmed a pure 1p36 duplication involving multiple genes.
Genetic testing should be considered in any pediatric patient with a history of multiple syndromic systemic findings, even if only mild ocular findings are present.
Genetic testing can aid in identifying a chromosomal anomaly, the genes involved, anticipated phenotypic severity and risk for relatives.1p36 duplication syndrome is one of the rarest genetic mutations, and the incidence of this pure duplication is unknown.¹
Phenotypes range from mild to severe with severe phenotypes having the highest mortality rate.²
Clinical phenotypes of a 1p36 duplication may include:
Craniosynostosis
Developmental delays
Autism
ADHD
Intellectual delays
Cardiac defects
Seizures
Myopia
Strabismus
Congenital cataract
Ptosis
Cloudy corneas
This patient was diagnosed with a mild phenotype of 1p36 duplication syndrome with a congenital heart defect, seizures, myopia, developmental and intellectual delays and ADHD.
However, 1p36 duplication involving the ATAD3A gene have a severe phenotype which is often fatal within 6 weeks of birth. Congenital cataracts and corneal clouding are often seen in these cases.²
Testing can help determine which specialties should evaluate the patient for various phenotypic expressions of the genes affected. Early and continued monitoring allows for timely intervention.
Treatment, Management:
This patient is followed regularly by:
Ophthalmology
Q6-12 months
monitor for myopia progression
myopia control will be considered as indicated
Pediatrics/Neurology
Q3 months
Monitor response to ADHD treatment
Monitor seizures
School-based recommendations/therapies
Cardiology
After diagnosis was monitored frequently
Now, q2years to monitor for progression of aortic stenosis
Surgical/medical intervention will be considered as indicated
Conclusion:
Clinicians should have a high level of suspicion for chromosomal anomalies in pediatric patients presenting with multiple systemic or ocular findings, even if they are mild.
Genetic testing is critical for diagnosis of this rare yet potentially fatal 1p36 duplication syndrome.
Timely identification of this syndrome allows for co-management with Cardiology, Neurology, Pediatrics, Genetics, and eye care providers to monitor for the development of severe phenotypes that require intervention.
Bibliography:
1) Giannikou K, et al.Further Delineation of novel 1p36 rearrangements by array-CGH analysis: Narrowing the breakpoints and clarifying the ‘extended’ phenotype. Gene 2012;506(2):360–8.
2) Gunning AC, et al. Recurrent de novo NAHR reciprocal duplications in the ATAD3 gene cluster cause a neurogenetic trait with perturbed cholesterol and mitochondrial metabolism. Am J Hum Genet 2020;106(2):272–9.
1p36 duplication syndrome is a rare, often significant, and potentially fatal chromosomal anomaly. Genetic testing and appropriate inter-disciplinary co-management are indicated to provide comprehensive care for children with various phenotypic manifestations of this syndrome.
Case History:
9 YO Male
Chief complaint:
Blurry distance vision
Ocular History:
Compound Myopic Astigmatism (CMA)
Medical history:
ADHD
Developmental/Intellectual delays
Seizures
Subaortic stenosis
Family history:
None
Medications:
Adderall
Clonazepam
Pertinent Findings:
Clinical:
Mild increase in myopia
Good BCVA OD/OS
Other findings WNL OU
Radiology studies:
MRI Brain: No encephalopathy
Echocardiogram: Mild subaortic stenosis
Electroencephalography: Childhood epilepsy
Genetic testing:
Chromosomal Microarray:
Pure 1p36 duplication
Involving genes of potential clinical significance including NADK, GNB1, CALML6, TMEM52, KIAA1751, GABRD, PRKCZ, C1orf86, SKI, MORN1, LOC100129534
Differential Diagnosis:
Genetic syndromes:
1p36 duplication syndrome
Fragile X syndrome
Cri-du-chat syndrome
Angelman syndrome
Non-syndromic concurrent cardiac, neurologic, psychologic findings and refractive error
Diagnosis & Discussion:
Genetic testing with chromosomal microarray confirmed a pure 1p36 duplication involving multiple genes.
Genetic testing should be considered in any pediatric patient with a history of multiple syndromic systemic findings, even if only mild ocular findings are present.
Genetic testing can aid in identifying a chromosomal anomaly, the genes involved, anticipated phenotypic severity and risk for relatives.1p36 duplication syndrome is one of the rarest genetic mutations, and the incidence of this pure duplication is unknown.¹
Phenotypes range from mild to severe with severe phenotypes having the highest mortality rate.²
Clinical phenotypes of a 1p36 duplication may include:
Craniosynostosis
Developmental delays
Autism
ADHD
Intellectual delays
Cardiac defects
Seizures
Myopia
Strabismus
Congenital cataract
Ptosis
Cloudy corneas
This patient was diagnosed with a mild phenotype of 1p36 duplication syndrome with a congenital heart defect, seizures, myopia, developmental and intellectual delays and ADHD.
However, 1p36 duplication involving the ATAD3A gene have a severe phenotype which is often fatal within 6 weeks of birth. Congenital cataracts and corneal clouding are often seen in these cases.²
Testing can help determine which specialties should evaluate the patient for various phenotypic expressions of the genes affected. Early and continued monitoring allows for timely intervention.
Treatment, Management:
This patient is followed regularly by:
Ophthalmology
Q6-12 months
monitor for myopia progression
myopia control will be considered as indicated
Pediatrics/Neurology
Q3 months
Monitor response to ADHD treatment
Monitor seizures
School-based recommendations/therapies
Cardiology
After diagnosis was monitored frequently
Now, q2years to monitor for progression of aortic stenosis
Surgical/medical intervention will be considered as indicated
Conclusion:
Clinicians should have a high level of suspicion for chromosomal anomalies in pediatric patients presenting with multiple systemic or ocular findings, even if they are mild.
Genetic testing is critical for diagnosis of this rare yet potentially fatal 1p36 duplication syndrome.
Timely identification of this syndrome allows for co-management with Cardiology, Neurology, Pediatrics, Genetics, and eye care providers to monitor for the development of severe phenotypes that require intervention.
Bibliography:
1) Giannikou K, et al.Further Delineation of novel 1p36 rearrangements by array-CGH analysis: Narrowing the breakpoints and clarifying the ‘extended’ phenotype. Gene 2012;506(2):360–8.
2) Gunning AC, et al. Recurrent de novo NAHR reciprocal duplications in the ATAD3 gene cluster cause a neurogenetic trait with perturbed cholesterol and mitochondrial metabolism. Am J Hum Genet 2020;106(2):272–9.
2020 Results from the Antibiotic Resistance Monitoring in Ocular micRoorganisms (ARMOR) Surveillance Study
Published 2021 by Christine M. Sanfilippo
Program Number: 215220
Article Type: Scientific Program
PURPOSE
Antibiotic resistance among bacteria is an ongoing concern in optometry. Ocular infections encountered during routine clinical practice are infrequently cultured, and treatment is often selected empirically based on knowledge of likely bacterial pathogens and their antibiotic susceptibility profiles. ARMOR is the only prospective, multicenter antibiotic resistance surveillance study in the US specific to common ocular bacterial pathogens. Herein, we report in vitro resistance data for ocular isolates collected in 2020 as part of this ongoing study.
METHODS
Participating centers across the US submitted clinically relevant ocular isolates of Staphylococcus aureus, coagulase-negative staphylococci (CoNS), Streptococcus pneumoniae, Pseudomonas aeruginosa, and Haemophilus influenzae to an independent central laboratory for in vitro susceptibility testing. Minimum inhibitory concentrations (MICs; µg/mL) against various antibiotics were determined, and isolates were classified as susceptible, intermediate, or resistant per Clinical and Laboratory Standards Institute methodology and interpretive criteria, where available. Oxacillin was used to determine methicillin susceptibility/resistance phenotype of staphylococcal isolates.
RESULTS
A total of 598 isolates were collected from 25 participating US sites across 17 states in 2020. Resistance was observed among S. aureus (n=216) and CoNS (n=233), and was greatest for azithromycin (57% and 59%), oxacillin (33% and 43%), and ciprofloxacin (32% and 25%), respectively; 29% of CoNS strains were also resistant to trimethoprim. Multidrug resistance (MDR; resistance to ≥3 drug classes) was observed in 33% of S. aureus and 40% of CoNS, and in 73% and 76% of methicillin-resistant isolates thereof, respectively. Isolates of S. pneumoniae exhibited resistance to azithromycin, tetracycline, and oral penicillin (n=23; 48%, 43%, and 35%, respectively), with no resistance to other tested antibacterial agents. All 110 P. aeruginosa strains were resistant to polymyxin B (100%), although resistance to other tested drugs was ≤5%. No resistance was detected among the 16 H. influenzae isolates collected.
CONCLUSION
Surveillance results for 2020 from the ARMOR study indicate high levels antibiotic resistance to numerous agents among staphylococci, with MDR especially prevalent in methicillin-resistant strains. Results also demonstrate moderate resistance to a few agents among pneumococci, and low resistance among Gram-negative organisms (except for limited polymyxin B potency against P. aeruginosa isolates). Since in vitro resistance may foreshadow treatment failure, these surveillance data can serve as an important source of clinically useful information for empiric therapy decision-making.
Antibiotic resistance among bacteria is an ongoing concern in optometry. Ocular infections encountered during routine clinical practice are infrequently cultured, and treatment is often selected empirically based on knowledge of likely bacterial pathogens and their antibiotic susceptibility profiles. ARMOR is the only prospective, multicenter antibiotic resistance surveillance study in the US specific to common ocular bacterial pathogens. Herein, we report in vitro resistance data for ocular isolates collected in 2020 as part of this ongoing study.
METHODS
Participating centers across the US submitted clinically relevant ocular isolates of Staphylococcus aureus, coagulase-negative staphylococci (CoNS), Streptococcus pneumoniae, Pseudomonas aeruginosa, and Haemophilus influenzae to an independent central laboratory for in vitro susceptibility testing. Minimum inhibitory concentrations (MICs; µg/mL) against various antibiotics were determined, and isolates were classified as susceptible, intermediate, or resistant per Clinical and Laboratory Standards Institute methodology and interpretive criteria, where available. Oxacillin was used to determine methicillin susceptibility/resistance phenotype of staphylococcal isolates.
RESULTS
A total of 598 isolates were collected from 25 participating US sites across 17 states in 2020. Resistance was observed among S. aureus (n=216) and CoNS (n=233), and was greatest for azithromycin (57% and 59%), oxacillin (33% and 43%), and ciprofloxacin (32% and 25%), respectively; 29% of CoNS strains were also resistant to trimethoprim. Multidrug resistance (MDR; resistance to ≥3 drug classes) was observed in 33% of S. aureus and 40% of CoNS, and in 73% and 76% of methicillin-resistant isolates thereof, respectively. Isolates of S. pneumoniae exhibited resistance to azithromycin, tetracycline, and oral penicillin (n=23; 48%, 43%, and 35%, respectively), with no resistance to other tested antibacterial agents. All 110 P. aeruginosa strains were resistant to polymyxin B (100%), although resistance to other tested drugs was ≤5%. No resistance was detected among the 16 H. influenzae isolates collected.
CONCLUSION
Surveillance results for 2020 from the ARMOR study indicate high levels antibiotic resistance to numerous agents among staphylococci, with MDR especially prevalent in methicillin-resistant strains. Results also demonstrate moderate resistance to a few agents among pneumococci, and low resistance among Gram-negative organisms (except for limited polymyxin B potency against P. aeruginosa isolates). Since in vitro resistance may foreshadow treatment failure, these surveillance data can serve as an important source of clinically useful information for empiric therapy decision-making.
30-degree Ultrasound test in Pseudo-Foster Kennedy Syndrome
Published 2021 by Beth Harper
Program Number: 215192
Article Type: Scientific Program
PURPOSE
Pseudo-Foster Kennedy syndrome (PFKS) is characterized by unilateral optic atrophy with contralateral optic nerve head edema, in the absence of an intracranial mass. This rare syndrome can be caused by numerous conditions including increased intracranial pressure from non-mass causes. Diagnosing PFKS often requires utilization of multiple tests. This case highlights the utility of the 30-degree ultrasound test in the diagnosis of complicated PFKS where papilledema was suspected but confirmatory lumbar puncture was contraindicated. The 30-degree test provides useful analysis of retrobulbar optic nerve sheath diameter and the presence or absence of excessive fluid in the sheath.
CASE REPORT
A 79 year old white male with a history of aortic valve replacement, BPH, dyslipidemia, obstructive sleep apnea and managed hypertension presented to the Optometry clinic complaining of sudden onset painless vision loss OD x 1 week. The fellow optic nerve had longstanding atrophy since 2005 from suspected NAION. BCVA were 20/20 in the involved right eye and 20/150 in the left. Exam revealed right eye inferior and superior sectoral disc edema in a normal sized disc, with nasal flame hemorrhages. A mild RAPD was present OS. The patient denied headache, jaw claudication, nausea, or weight loss, but reported increasing end-of-day fatigue for several months. Visual field testing OD revealed 360-degree constriction with increased density inferior nasal.
Differentials included AION and papilledema based on nerve appearance and visual fields. Urgent ESR, CSR and MRI were ordered. ESR and CRP returned normal, reducing suspicion for AION. Head CT and MRA of head/neck were normal. MRI was negative for intracranial mass, hemorrhage, or hydrocephalus. There was increased CSF fluid surrounding the left optic nerve compared to the right. Neuro-ophthalmology was consulted, diagnosed NAION and discharged the pt. He returned to our clinic 10 days later and repeat VF demonstrated worsening of the defects. Suspicion for papilledema prompted orders for a 30-degree test. Results yielded OD: 5.58mm and OS: 5.54mm, considerably large, and 30-degree test was positive with 26% change OD and 23% change OS. After viewing our findings, neuro-ophthalmology agreed with the diagnosis of papilledema. Due to patient’s chronic anticoagulation, he elected empirical treatment with Diamox. Within two weeks, the pt reported noticeable reduction in symptoms. OD VF Mean deviation also markedly improved. He remained on Diamox for 3 months, then discontinued and was lost to follow up. 6 months later he returned with complaints of a new blurred spot. Diamox was restarted, and again a reduction in VF MD occurred along with improvement in symptoms. His poorly controlled obstructive sleep apnea is presumed responsible for his condition; he is being maintained on Diamox 500mg BID.
CONCLUSION
This case highlights the utility of 30-degree US test in evaluating complicated PFKS in cases where lumbar puncture is contraindicated.
Pseudo-Foster Kennedy syndrome (PFKS) is characterized by unilateral optic atrophy with contralateral optic nerve head edema, in the absence of an intracranial mass. This rare syndrome can be caused by numerous conditions including increased intracranial pressure from non-mass causes. Diagnosing PFKS often requires utilization of multiple tests. This case highlights the utility of the 30-degree ultrasound test in the diagnosis of complicated PFKS where papilledema was suspected but confirmatory lumbar puncture was contraindicated. The 30-degree test provides useful analysis of retrobulbar optic nerve sheath diameter and the presence or absence of excessive fluid in the sheath.
CASE REPORT
A 79 year old white male with a history of aortic valve replacement, BPH, dyslipidemia, obstructive sleep apnea and managed hypertension presented to the Optometry clinic complaining of sudden onset painless vision loss OD x 1 week. The fellow optic nerve had longstanding atrophy since 2005 from suspected NAION. BCVA were 20/20 in the involved right eye and 20/150 in the left. Exam revealed right eye inferior and superior sectoral disc edema in a normal sized disc, with nasal flame hemorrhages. A mild RAPD was present OS. The patient denied headache, jaw claudication, nausea, or weight loss, but reported increasing end-of-day fatigue for several months. Visual field testing OD revealed 360-degree constriction with increased density inferior nasal.
Differentials included AION and papilledema based on nerve appearance and visual fields. Urgent ESR, CSR and MRI were ordered. ESR and CRP returned normal, reducing suspicion for AION. Head CT and MRA of head/neck were normal. MRI was negative for intracranial mass, hemorrhage, or hydrocephalus. There was increased CSF fluid surrounding the left optic nerve compared to the right. Neuro-ophthalmology was consulted, diagnosed NAION and discharged the pt. He returned to our clinic 10 days later and repeat VF demonstrated worsening of the defects. Suspicion for papilledema prompted orders for a 30-degree test. Results yielded OD: 5.58mm and OS: 5.54mm, considerably large, and 30-degree test was positive with 26% change OD and 23% change OS. After viewing our findings, neuro-ophthalmology agreed with the diagnosis of papilledema. Due to patient’s chronic anticoagulation, he elected empirical treatment with Diamox. Within two weeks, the pt reported noticeable reduction in symptoms. OD VF Mean deviation also markedly improved. He remained on Diamox for 3 months, then discontinued and was lost to follow up. 6 months later he returned with complaints of a new blurred spot. Diamox was restarted, and again a reduction in VF MD occurred along with improvement in symptoms. His poorly controlled obstructive sleep apnea is presumed responsible for his condition; he is being maintained on Diamox 500mg BID.
CONCLUSION
This case highlights the utility of 30-degree US test in evaluating complicated PFKS in cases where lumbar puncture is contraindicated.
5 Secrets for Sports Vision Success in the Primary Care Practice
Published 2021 by Fraser Horn
Article Type: Lectures & Workshops
In primary care practice, we have the opportunity to make small changes that can make a significant improvement in vision and possibly athletic/recreational performance. We will discuss five “secrets” to help integrate foundational and evidence-based aspects of sports and performance vision into your practice. We will provide case examples and this should help with taking the first steps towards helping your patients.
A Case of Bilateral Pars Planitis
Published 2021 by Paige Carr
Article Type: Residents Day
Abstract:
A 31 year old patient complains of black lines in his vision OU and photophobia. Upon examination, he is diagnosed with bilateral pars planitis. Labs and radiology studies reveal a likely idiopathic origin.
Case History:
Patient demographics: 31 year old mixed race male
Chief complaint: black lines in his vision OU, photophobia
Ocular, medical history: a history of acute anterior uveitis OS eight months prior
Medications: none
Pertinent Findings:
Clinical: His entering visual acuities were 20/30 OD and 20/40-1 OS uncorrected. Entrance testing was otherwise normal. Intraocular pressures were 17/17 mmHg OD and OS. The slit lamp examination revealed the anterior chambers OU were deep with 1+ cell and 2+ flare. There were pigment clumps on the anterior capsule OS. The conjunctiva was white and quiet OU. The anterior vitreous had 2+ cells with haze (indicating 2+ vitritis) OU. On the retina, there extensive snowbanking with snowballs inferiorly OU, indicating settled white blood cells in the posterior vitreous obscuring the inferior retinae. Fluorescein angiography revealed pars planitis OU, optic disc leakage OU, and increased choroidal and vascular permeability (with no vasculitis or retinitis seen). Fundus photos revealed pars planitis OU with snowballs inferiorly. A macular OCT revealed retinal thickening associated with cystoid macular edema OU.
Laboratory studies: bloodwork (CBC with differential, sed rate, ACE, RPE, CRP, blood chemistry) within normal limits
Radiology studies: chest x-ray within normal limits
Differential Diagnosis:
Primary/leading: pars planitis OU
Others: panuveitis OU
Diagnosis & Discussion:
Pars planitis is an intermediate uveitis defined as the inflammation of the anterior vitreous, ciliary body, and peripheral retina (Ozdal et al). Its incidence within all of uveitis patients is from 2.4 to 15.4%, and it is characterized clinically by snowballs and snowbank exudates in the vitreous (the latter caused by glial cell proliferation after inflammation), with sequelae that could include cystoid macular edema, disc edema, retinal vasculitis, cataract, epiretinal membrane, and more. Histology suggests that the cause is likely autoimmune due to the presence of helper T cells in the snowbanks, or genetic due to the presence of certain human leukocyte antigen alleles. Several HLA alleles have been associated, including, but not limited to, HLA-DR15 (Przeździecka-Dołyk et al). Peer reviewed literature from Western publications estimates bilaterality at 70-90%. Symptom presentation often includes complaints of floaters, blurred or lost vision (Babu et al).
Treatment, Management:
The patient was prescribed Pred Forte QID OU, then switched to Durezol QID OU. He received a subTenon’s Kenalog injection OU with a follow-up appointment scheduled for 9/17/21. If drug therapy fails, subsequent treatments may include systemic NSAIDs or steroids, immunosuppressive treatments, anti tumor-necrosis-factor-⍺ agents, pars plana vitrectomy, and/or laser photocoagulation (Ozdal et al, Przeździecka-Dołyk et al).
Conclusion:
Pars planitis is an intermediate uveitis defined as the inflammation of the anterior vitreous, ciliary body, and peripheral retina. It is often bilateral and is hypothesized to be due to an autoimmune or genetic process.
The condition is characterized clinically by snowballs and snowbank exudates in the vitreous, with numerous possible retinal sequelae including cystoid macular edema.
Management begins with excluding systemic etiologies. The first line treatment is usually periocular corticosteroid injection.
Bibliography:
Babu BM, Rathinam SR. Intermediate uveitis. Indian J Ophthalmol. 2010;58(1):21-27. doi:10.4103/0301-4738.58469
Ozdal PC, Berker N, Tugal-Tutkun I. Pars Planitis: Epidemiology, Clinical Characteristics, Management and Visual Prognosis. J Ophthalmic Vis Res. 2015;10(4):469-480. doi:10.4103/2008-322X.176897
Przeździecka-Dołyk J, Węgrzyn A, Turno-Kręcicka A, Misiuk-Hojło M. Immunopathogenic Background of Pars Planitis. Arch Immunol Ther Exp (Warsz). 2016;64(2):127-137. doi:10.1007/s00005-015-0361-y
A 31 year old patient complains of black lines in his vision OU and photophobia. Upon examination, he is diagnosed with bilateral pars planitis. Labs and radiology studies reveal a likely idiopathic origin.
Case History:
Patient demographics: 31 year old mixed race male
Chief complaint: black lines in his vision OU, photophobia
Ocular, medical history: a history of acute anterior uveitis OS eight months prior
Medications: none
Pertinent Findings:
Clinical: His entering visual acuities were 20/30 OD and 20/40-1 OS uncorrected. Entrance testing was otherwise normal. Intraocular pressures were 17/17 mmHg OD and OS. The slit lamp examination revealed the anterior chambers OU were deep with 1+ cell and 2+ flare. There were pigment clumps on the anterior capsule OS. The conjunctiva was white and quiet OU. The anterior vitreous had 2+ cells with haze (indicating 2+ vitritis) OU. On the retina, there extensive snowbanking with snowballs inferiorly OU, indicating settled white blood cells in the posterior vitreous obscuring the inferior retinae. Fluorescein angiography revealed pars planitis OU, optic disc leakage OU, and increased choroidal and vascular permeability (with no vasculitis or retinitis seen). Fundus photos revealed pars planitis OU with snowballs inferiorly. A macular OCT revealed retinal thickening associated with cystoid macular edema OU.
Laboratory studies: bloodwork (CBC with differential, sed rate, ACE, RPE, CRP, blood chemistry) within normal limits
Radiology studies: chest x-ray within normal limits
Differential Diagnosis:
Primary/leading: pars planitis OU
Others: panuveitis OU
Diagnosis & Discussion:
Pars planitis is an intermediate uveitis defined as the inflammation of the anterior vitreous, ciliary body, and peripheral retina (Ozdal et al). Its incidence within all of uveitis patients is from 2.4 to 15.4%, and it is characterized clinically by snowballs and snowbank exudates in the vitreous (the latter caused by glial cell proliferation after inflammation), with sequelae that could include cystoid macular edema, disc edema, retinal vasculitis, cataract, epiretinal membrane, and more. Histology suggests that the cause is likely autoimmune due to the presence of helper T cells in the snowbanks, or genetic due to the presence of certain human leukocyte antigen alleles. Several HLA alleles have been associated, including, but not limited to, HLA-DR15 (Przeździecka-Dołyk et al). Peer reviewed literature from Western publications estimates bilaterality at 70-90%. Symptom presentation often includes complaints of floaters, blurred or lost vision (Babu et al).
Treatment, Management:
The patient was prescribed Pred Forte QID OU, then switched to Durezol QID OU. He received a subTenon’s Kenalog injection OU with a follow-up appointment scheduled for 9/17/21. If drug therapy fails, subsequent treatments may include systemic NSAIDs or steroids, immunosuppressive treatments, anti tumor-necrosis-factor-⍺ agents, pars plana vitrectomy, and/or laser photocoagulation (Ozdal et al, Przeździecka-Dołyk et al).
Conclusion:
Pars planitis is an intermediate uveitis defined as the inflammation of the anterior vitreous, ciliary body, and peripheral retina. It is often bilateral and is hypothesized to be due to an autoimmune or genetic process.
The condition is characterized clinically by snowballs and snowbank exudates in the vitreous, with numerous possible retinal sequelae including cystoid macular edema.
Management begins with excluding systemic etiologies. The first line treatment is usually periocular corticosteroid injection.
Bibliography:
Babu BM, Rathinam SR. Intermediate uveitis. Indian J Ophthalmol. 2010;58(1):21-27. doi:10.4103/0301-4738.58469
Ozdal PC, Berker N, Tugal-Tutkun I. Pars Planitis: Epidemiology, Clinical Characteristics, Management and Visual Prognosis. J Ophthalmic Vis Res. 2015;10(4):469-480. doi:10.4103/2008-322X.176897
Przeździecka-Dołyk J, Węgrzyn A, Turno-Kręcicka A, Misiuk-Hojło M. Immunopathogenic Background of Pars Planitis. Arch Immunol Ther Exp (Warsz). 2016;64(2):127-137. doi:10.1007/s00005-015-0361-y
A Case of Bilateral Trochleitis Masquerading as Convergence Insufficiency
Published 2021 by Colin Kane
Article Type: Residents Day
Abstract:
Trochleitis is a rare condition causing periorbital pain that may masquerade as headache or asthenopia. This case reveals bilateral trochleitis following traumatic brain injury that was initially attributed to asthenopia caused by post-concussion convergence insufficiency.
Case History:
63 YO AAF with a Hx of well controlled hypertension and hyperlipidemia suffered a TBI in an MVA. Her tractor-trailer truck transporting fluid was struck from behind, causing her to repeatedly hit her head against her steering wheel and headrest before losing consciousness. Days later, she developed diffuse headaches (HA), trouble reading with associated left forehead pain, and diplopia in lateral gazes. Her Neurologist prescribed butalbital and amantadine for her HA, which improved since the accident, though her eye pain remained. She was then referred to the BV clinic for evaluation and was diagnosed with convergence insufficiency (CI). Prism glasses and vision therapy (VT) were prescribed. After 15 VT sessions, her CI improved though she continued experiencing the same symptoms. She was then referred to Neuro-Optometry.
Differentail Diagnosis:
Trochleitis, Acquired Brown Syndrome, Sinusitis, Paroxysmal Hemicrania, Orbital Myositis
Diagnosis & Discussion:
Trochleitis (now considered within the same clinical spectrum as primary trochlear HA and trochleodynia), is a rare and likely underdiagnosed condition that may easily be mistaken for HA or asthenopia. The ST nerve, a branch of the trigeminal nerve, runs closely anterosuperior to the trochlea and supraorbital tendon. In trochleitis, the inflamed trochlea is believed to stimulate the nociceptive portion of the ST nerve through repetitive agitation of the trochlea from the superior oblique tendon with eye movements. Most cases are unilateral and idiopathic, though trochleitis can be secondary to sinusitis, trauma or, more rarely, rheumatologic or autoimmune etiologies(1,2). The onset of symptoms in our patient occurred shortly after repeated frontal head injury, suggesting post-traumatic trochleitis.
The diagnosis of trochleitis is largely clinical, as approximately only 20% present with CT or MRI findings(1). Focal tenderness on palpation of the ST notch and medial 1/3rd of the forehead is nearly pathognomonic for trochleitis and highly suggested this diagnosis in our patient. Pain occurs during adduction of the eye in lateral gaze and with convergence while reading, which our patient reported. Mechanical restriction of the eye and diplopia are less common findings, reported in 14% and 12% of cases, respectively(3).
Treatment, Management:
Oral analgesics are the initial treatment for mild cases, though this was unsuccessful in our patient. We referred her to Oculoplastics where she was offered periorbital steroid injection and elected to proceed. 20 mL of Kenalog 40mg/mL was injected into the superonasal orbit. She returned a month later, reporting an initial significant improvement though now with mild superonasal pain bilaterally. She was diagnosed with bilateral trochleitis and a steroid injection was performed in both orbits. She was to RTC if symptoms worsen or fail to improve, and she has not returned.
Conclusion:
Trochleitis is an underrecognized clinical entity that can present in isolation or concurrently with other HA spectra and may exacerbate those conditions(1,2). The clinical findings of tenderness on palpation of the ST notch and distribution are highly specific and should be investigated in patients with HA that does not respond to traditional therapy.
Bibliography:
1.Tran TM et al. Diagnosis and Management of Trochleodynia, Trochleitis, and Trochlear Headache. Front Neurol. 2019;10:361. Published 2019 Apr 12
2.Yangüela J et al. Primary trochlear headache: a new cephalgia generated and modulated on the trochlear region. Neurology. 2004;62(7):1134-1140
3.Jarrín E et al. Clinical Characteristics, Treatment, and Outcome of Trochleitis. Strabismus. 2017;25(1):1-4
Trochleitis is a rare condition causing periorbital pain that may masquerade as headache or asthenopia. This case reveals bilateral trochleitis following traumatic brain injury that was initially attributed to asthenopia caused by post-concussion convergence insufficiency.
Case History:
63 YO AAF with a Hx of well controlled hypertension and hyperlipidemia suffered a TBI in an MVA. Her tractor-trailer truck transporting fluid was struck from behind, causing her to repeatedly hit her head against her steering wheel and headrest before losing consciousness. Days later, she developed diffuse headaches (HA), trouble reading with associated left forehead pain, and diplopia in lateral gazes. Her Neurologist prescribed butalbital and amantadine for her HA, which improved since the accident, though her eye pain remained. She was then referred to the BV clinic for evaluation and was diagnosed with convergence insufficiency (CI). Prism glasses and vision therapy (VT) were prescribed. After 15 VT sessions, her CI improved though she continued experiencing the same symptoms. She was then referred to Neuro-Optometry.
Differentail Diagnosis:
Trochleitis, Acquired Brown Syndrome, Sinusitis, Paroxysmal Hemicrania, Orbital Myositis
Diagnosis & Discussion:
Trochleitis (now considered within the same clinical spectrum as primary trochlear HA and trochleodynia), is a rare and likely underdiagnosed condition that may easily be mistaken for HA or asthenopia. The ST nerve, a branch of the trigeminal nerve, runs closely anterosuperior to the trochlea and supraorbital tendon. In trochleitis, the inflamed trochlea is believed to stimulate the nociceptive portion of the ST nerve through repetitive agitation of the trochlea from the superior oblique tendon with eye movements. Most cases are unilateral and idiopathic, though trochleitis can be secondary to sinusitis, trauma or, more rarely, rheumatologic or autoimmune etiologies(1,2). The onset of symptoms in our patient occurred shortly after repeated frontal head injury, suggesting post-traumatic trochleitis.
The diagnosis of trochleitis is largely clinical, as approximately only 20% present with CT or MRI findings(1). Focal tenderness on palpation of the ST notch and medial 1/3rd of the forehead is nearly pathognomonic for trochleitis and highly suggested this diagnosis in our patient. Pain occurs during adduction of the eye in lateral gaze and with convergence while reading, which our patient reported. Mechanical restriction of the eye and diplopia are less common findings, reported in 14% and 12% of cases, respectively(3).
Treatment, Management:
Oral analgesics are the initial treatment for mild cases, though this was unsuccessful in our patient. We referred her to Oculoplastics where she was offered periorbital steroid injection and elected to proceed. 20 mL of Kenalog 40mg/mL was injected into the superonasal orbit. She returned a month later, reporting an initial significant improvement though now with mild superonasal pain bilaterally. She was diagnosed with bilateral trochleitis and a steroid injection was performed in both orbits. She was to RTC if symptoms worsen or fail to improve, and she has not returned.
Conclusion:
Trochleitis is an underrecognized clinical entity that can present in isolation or concurrently with other HA spectra and may exacerbate those conditions(1,2). The clinical findings of tenderness on palpation of the ST notch and distribution are highly specific and should be investigated in patients with HA that does not respond to traditional therapy.
Bibliography:
1.Tran TM et al. Diagnosis and Management of Trochleodynia, Trochleitis, and Trochlear Headache. Front Neurol. 2019;10:361. Published 2019 Apr 12
2.Yangüela J et al. Primary trochlear headache: a new cephalgia generated and modulated on the trochlear region. Neurology. 2004;62(7):1134-1140
3.Jarrín E et al. Clinical Characteristics, Treatment, and Outcome of Trochleitis. Strabismus. 2017;25(1):1-4
A Case of Choroidal Neovascularization in a Pediatric Patient with Best Disease
Published 2021 by Jia Yu Liu
Program Number: 215312
Article Type: Scientific Program
PURPOSE
Best vitelliform macular dystrophy, also known as Best disease is mostly an autosomal dominant disorder caused by mutations in the BEST1 gene. The pathophysiology for Best disease remains incomplete. BEST1 encodes for Best1 protein, which resides in the RPE and acts as a calcium-activated chloride channel. BEST1 mutations are thought to disrupt ionic transport of the protein, leading to accumulation of fluid between RPE and photoreceptors, which in turn leads to accumulation of lipofuscin and impaired RPE function. Best disease is often diagnosed in childhood with mildly decreased central vision even in the presence of vitelliform lesions, however can be complicated by CNV which may lead to rapid decline in visual acuity. There is currently no treatment options for Best disease. Reported treatment procedures for CNV associated with Best disease include photodynamic therapy, laser photocoagulation, intravitreal triamcinolone, and intravitreal anti-VEGF agents. The purpose of this poster is to discuss the new role of optical coherence tomography angiography (OCTA) in diagnosing and characterizing Best disease, and to report the latest findings from current gene therapy research to treat Best disease.
METHODS
CASE REPORT
A 12 year-old female presented with a chief complaint of painless blurred vision in the left eye for two weeks. Best corrected visual acuity was 20/20-1 in her right eye and 20/100-1 in her left eye. Anterior segment examination was within normal limits in both eyes. Dilated fundus examination showed vitelliform egg yolk lesions in both eyes without hemorrhages. The patient was seen two weeks later in the retina service, where she developed CNV in the left eye evidently shown on OCTA, with subretinal hemorrhage. The patient received intravitreal Avastin in the left eye at the same visit.
RESULTS
CONCLUSION
Eyes with best disease were found to have certain characteristics on OCTA including abnormal foveal avascular zone (FAZ) in superficial and deep retinal layers, patchy vascularity loss in the deep layers, hypo-reflective center in the choriocapillary layer, and hypolucent area around the CNV complex in the outer retinal layer. OCTA was also noted to be superior to fluorescein angiography (FA) in measuring CNV, as the FA underestimates the amount of neovascular area due to the presence of vitelliform lesions which are also stained on FA. Research on gene augmentation for Best disease is ongoing. Li et al demonstrated that calcium-activated chloride channel in patient-derived induced pluripotent stem cells (iPSC)-RPEs carrying recessive BEST1 mutations can be rescued by baculovirus-mediated supplementation of the WT BEST1 gene. Another recent study by Guziewicz et al found loss of RPE microvilli and resulting micro-detachment of the retina in the canine BEST1 disease model, and demonstrated that subretinal adeno-associated virus-based gene therapy reversed both the vitelliform lesions as well as the micro-detachments.
ABSTRACT BODY
Best vitelliform macular dystrophy, also known as Best disease is mostly an autosomal dominant disorder caused by mutations in the BEST1 gene. The pathophysiology for Best disease remains incomplete. BEST1 encodes for Best1 protein, which resides in the RPE and acts as a calcium-activated chloride channel. BEST1 mutations are thought to disrupt ionic transport of the protein, leading to accumulation of fluid between RPE and photoreceptors, which in turn leads to accumulation of lipofuscin and impaired RPE function. Best disease is often diagnosed in childhood with mildly decreased central vision even in the presence of vitelliform lesions, however can be complicated by CNV which may lead to rapid decline in visual acuity. There is currently no treatment options for Best disease. Reported treatment procedures for CNV associated with Best disease include photodynamic therapy, laser photocoagulation, intravitreal triamcinolone, and intravitreal anti-VEGF agents. The purpose of this poster is to discuss the new role of optical coherence tomography angiography (OCTA) in diagnosing and characterizing Best disease, and to report the latest findings from current gene therapy research to treat Best disease.
METHODS
CASE REPORT
A 12 year-old female presented with a chief complaint of painless blurred vision in the left eye for two weeks. Best corrected visual acuity was 20/20-1 in her right eye and 20/100-1 in her left eye. Anterior segment examination was within normal limits in both eyes. Dilated fundus examination showed vitelliform egg yolk lesions in both eyes without hemorrhages. The patient was seen two weeks later in the retina service, where she developed CNV in the left eye evidently shown on OCTA, with subretinal hemorrhage. The patient received intravitreal Avastin in the left eye at the same visit.
RESULTS
CONCLUSION
Eyes with best disease were found to have certain characteristics on OCTA including abnormal foveal avascular zone (FAZ) in superficial and deep retinal layers, patchy vascularity loss in the deep layers, hypo-reflective center in the choriocapillary layer, and hypolucent area around the CNV complex in the outer retinal layer. OCTA was also noted to be superior to fluorescein angiography (FA) in measuring CNV, as the FA underestimates the amount of neovascular area due to the presence of vitelliform lesions which are also stained on FA. Research on gene augmentation for Best disease is ongoing. Li et al demonstrated that calcium-activated chloride channel in patient-derived induced pluripotent stem cells (iPSC)-RPEs carrying recessive BEST1 mutations can be rescued by baculovirus-mediated supplementation of the WT BEST1 gene. Another recent study by Guziewicz et al found loss of RPE microvilli and resulting micro-detachment of the retina in the canine BEST1 disease model, and demonstrated that subretinal adeno-associated virus-based gene therapy reversed both the vitelliform lesions as well as the micro-detachments.
ABSTRACT BODY
A Case of Incidental Bilateral Diffuse Retinal Atrophy
Published 2021 by Lor Sildiryan
Article Type: Lectures & Workshops
An asymptomatic 15-year-old Arabic female with history of post-surgical partially accommodative esotropia presents for her annual eye exam and dilated retinal exam shows diffuse retinal atrophy in both eyes.
A Case of Interstitial Keratitis Following Herpes Simplex Epithelial Dendritic Keratitis in the Contralateral Eye
Published 2021 by Alim Karmali
Article Type: Residents Day
Abstract:
Herpes Simplex Virus (HSV) is characteristically a unilateral infection. This case reviews its pathophysiology and ocular consequences, including Herpes Simplex Keratitis (HSK) and a unique onset of Interstitial Keratitis (IK) in the contralateral eye.
Case History:
An 11-year-old female presents in July 2021 for a 3-day follow-up with symptoms of moderate pain and redness OS and severely blurry vision OD for the past week. Current treatment is Vigamox Q2H OU and Valtrex 500mg TID PO prescribed at her initial visit. Ocular history significant for recurrent marginal keratitis (MK) OU suspected secondary to juvenile ocular rosacea since December 2020. Also notable was a past episode of MK OS in January 2021 which developed an opportunistic HSK dendrite after prolonged topical steroid use. Medical history positive for eczema, though unmedicated.
Pertinent Findings:
Entering VAs are 20/150 OD (PHNI) and 20/20 OS. Pupils are normal. IOPs are 11/10 mmHg via rebound tonometry. Slit lamp exam reveals several superior peripheral infiltrates, minimal meibomian gland expression, 1+ papillae, 2+ diffuse conjunctival hyperemia, and 1+ palpebral and bulbar conjunctival follicles OU. Diffuse stromal haze, mild microcystic edema, and 3+ SPK noted OD. Sterile peripheral ulcer (1x1mm) with 2mm adjacent corneal neovascularization OS; epithelial defect improved from previous visit (only 50% staining). No anterior chamber or posterior segment involvement OU.
Differential Diagnosis:
Recurrent marginal keratitis OU due to juvenile ocular rosacea causing secondary sterile peripheral ulcer OS, interstitial keratitis OD - likely HSV etiology.
Diagnosis & Discussion:
HSV is typically a unilateral infection of the trigeminal ganglion where it resides in a latent phase until activated, resulting in ipsilateral neuronal spread to the affected eye.1,2 Activation of the virus can produce ocular sequelae varying from corneal involvement, inflammation of the uveal tract, to vesicular conjunctival lesions.6 In this case, epithelial and interstitial keratitis are of relevance. HSV accounts for the vast majority of unilateral IK.3 Bilateral manifestation is less likely given its pathophysiology, with an incidence of only 1-12%.4,5 However, it is more prevalent in younger, immunocompromised, and atopic populations.1,4 Bilateral involvement can develop following independent primary infection or re-activation of both trigeminal ganglia, either from the same or a different variant.1 Alternatively, incomplete HSV immunity following the primary infection can allow for re-infection of the contralateral eye.1
Treatment, Management:
Added Pred Forte Q2H OD. Maintained Valtrex 500mg TID and Vigamox Q2H OU. Follow-up in 3 days. At subsequent visits, Vigamox dosing was reduced to QID OU, Lotemax Gel was introduced QID OS upon further re-epithelialization of the ulcer. Full resolution occurred after 15 days; VA OD returned to 20/20.
Conclusion:
The consequences of HSK can be significant and visually devastating. While rare, this case demonstrates an instance of bilateral HSV activation and explores the mechanism behind it. It further emphasizes the importance of recognizing rare presentations of disease and initiating aggressive therapeutic interventions to prevent permanent damage or vision loss.
Bibliography:
1. Wilhelmus, K. R., Falcon, M. G., & Jones, B. R. (1981). Bilateral herpetic keratitis. British Journal of Ophthalmology, 65(6), 385-387.
2. Farooq, A. V., & Shukla, D. (2012). Herpes simplex epithelial and stromal keratitis: an epidemiologic update. Survey of ophthalmology, 57(5), 448-462.
3. Schwartz, G. S., Harrison, A. R., & Holland, E. J. (1998). Etiology of immune stromal (interstitial) keratitis. Cornea, 17(3), 278–281.
4. Holland, E. J., & Huang, A. J. (2003). Bilateral herpetic keratoconjunctivitis. Ophthalmology, 110(3), 493-496.
5. Kitzmann, A. S., Goins, K. M., Syed, N. A., & Wagoner, M. D. (2008). Bilateral herpes simplex keratitis with unilateral secondary bacterial keratitis and corneal perforation in a patient with pityriasis rubra pilaris. Cornea, 27(10), 1212-1214.
6. Valerio, G. S., & Lin, C. C. (2019). Ocular manifestations of herpes simplex virus. Current opinion in ophthalmology, 30(6), 525-531.
Herpes Simplex Virus (HSV) is characteristically a unilateral infection. This case reviews its pathophysiology and ocular consequences, including Herpes Simplex Keratitis (HSK) and a unique onset of Interstitial Keratitis (IK) in the contralateral eye.
Case History:
An 11-year-old female presents in July 2021 for a 3-day follow-up with symptoms of moderate pain and redness OS and severely blurry vision OD for the past week. Current treatment is Vigamox Q2H OU and Valtrex 500mg TID PO prescribed at her initial visit. Ocular history significant for recurrent marginal keratitis (MK) OU suspected secondary to juvenile ocular rosacea since December 2020. Also notable was a past episode of MK OS in January 2021 which developed an opportunistic HSK dendrite after prolonged topical steroid use. Medical history positive for eczema, though unmedicated.
Pertinent Findings:
Entering VAs are 20/150 OD (PHNI) and 20/20 OS. Pupils are normal. IOPs are 11/10 mmHg via rebound tonometry. Slit lamp exam reveals several superior peripheral infiltrates, minimal meibomian gland expression, 1+ papillae, 2+ diffuse conjunctival hyperemia, and 1+ palpebral and bulbar conjunctival follicles OU. Diffuse stromal haze, mild microcystic edema, and 3+ SPK noted OD. Sterile peripheral ulcer (1x1mm) with 2mm adjacent corneal neovascularization OS; epithelial defect improved from previous visit (only 50% staining). No anterior chamber or posterior segment involvement OU.
Differential Diagnosis:
Recurrent marginal keratitis OU due to juvenile ocular rosacea causing secondary sterile peripheral ulcer OS, interstitial keratitis OD - likely HSV etiology.
Diagnosis & Discussion:
HSV is typically a unilateral infection of the trigeminal ganglion where it resides in a latent phase until activated, resulting in ipsilateral neuronal spread to the affected eye.1,2 Activation of the virus can produce ocular sequelae varying from corneal involvement, inflammation of the uveal tract, to vesicular conjunctival lesions.6 In this case, epithelial and interstitial keratitis are of relevance. HSV accounts for the vast majority of unilateral IK.3 Bilateral manifestation is less likely given its pathophysiology, with an incidence of only 1-12%.4,5 However, it is more prevalent in younger, immunocompromised, and atopic populations.1,4 Bilateral involvement can develop following independent primary infection or re-activation of both trigeminal ganglia, either from the same or a different variant.1 Alternatively, incomplete HSV immunity following the primary infection can allow for re-infection of the contralateral eye.1
Treatment, Management:
Added Pred Forte Q2H OD. Maintained Valtrex 500mg TID and Vigamox Q2H OU. Follow-up in 3 days. At subsequent visits, Vigamox dosing was reduced to QID OU, Lotemax Gel was introduced QID OS upon further re-epithelialization of the ulcer. Full resolution occurred after 15 days; VA OD returned to 20/20.
Conclusion:
The consequences of HSK can be significant and visually devastating. While rare, this case demonstrates an instance of bilateral HSV activation and explores the mechanism behind it. It further emphasizes the importance of recognizing rare presentations of disease and initiating aggressive therapeutic interventions to prevent permanent damage or vision loss.
Bibliography:
1. Wilhelmus, K. R., Falcon, M. G., & Jones, B. R. (1981). Bilateral herpetic keratitis. British Journal of Ophthalmology, 65(6), 385-387.
2. Farooq, A. V., & Shukla, D. (2012). Herpes simplex epithelial and stromal keratitis: an epidemiologic update. Survey of ophthalmology, 57(5), 448-462.
3. Schwartz, G. S., Harrison, A. R., & Holland, E. J. (1998). Etiology of immune stromal (interstitial) keratitis. Cornea, 17(3), 278–281.
4. Holland, E. J., & Huang, A. J. (2003). Bilateral herpetic keratoconjunctivitis. Ophthalmology, 110(3), 493-496.
5. Kitzmann, A. S., Goins, K. M., Syed, N. A., & Wagoner, M. D. (2008). Bilateral herpes simplex keratitis with unilateral secondary bacterial keratitis and corneal perforation in a patient with pityriasis rubra pilaris. Cornea, 27(10), 1212-1214.
6. Valerio, G. S., & Lin, C. C. (2019). Ocular manifestations of herpes simplex virus. Current opinion in ophthalmology, 30(6), 525-531.
A Case of Post-Operative Cataract Surgery Complications
Published 2021 by Jessica Yuen
Article Type: Lectures & Workshops
This case report presents a 75-year-old female diagnosed with uveitis-glaucoma-hyphema (UGH) syndrome secondary to an iris-suture posterior chamber intraocular lens. The etiology, diagnosis with ancillary testing, and management of UGH syndrome will be explored with an emphasis on early identification to reduce the development visually devastating effects and unnecessary lab testing. In addition, this case will discuss secondary intraocular lens placement and perioperative cataract complications associated with exfoliation syndrome.
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