Limits...
Spectrum of ocular manifestations in CLN2-associated batten (Jansky-Bielschowsky) disease correlate with advancing age and deteriorating neurological function.

Orlin A, Sondhi D, Witmer MT, Wessel MM, Mezey JG, Kaminsky SM, Hackett NR, Yohay K, Kosofsky B, Souweidane MM, Kaplitt MG, D'Amico DJ, Crystal RG, Kiss S - PLoS ONE (2013)

Bottom Line: Significantly more severe ophthalmic manifestations were observed among older patients (p<0.005) and patients with more severe neurological findings (p<0.03).A direct correlation was found between the Ophthalmic Severity Scale and the Weill Cornell Neurological Scale (p<0.002).A direct association was also found between age and the ophthalmic manifestations (p<0.0002), with older children having more severe ophthalmic manifestations.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Weill Cornell Medical College, New York, New York, United States of America.

ABSTRACT

Background: Late infantile neuronal ceroid lipofuscinosis (LINCL), one form of Batten's disease is a progressive neurodegenerative disorder resulting from a CLN2 gene mutation. The spectrum of ophthalmic manifestations of LINCL and the relationship with neurological function has not been previously described.

Methods: Patients underwent ophthalmic evaluations, including anterior segment and dilated exams, optical coherence tomography, fluorescein and indocyanine green angiography. Patients were also assessed with the LINCL Neurological Severity Scale. Ophthalmic findings were categorized into one of five severity scores, and the association of the extent of ocular disease with neurological function was assessed.

Results: Fifty eyes of 25 patients were included. The mean age at the time of exam was 4.9 years (range 2.5 to 8.1). The mean ophthalmic severity score was 2.6 (range 1 to 5). The mean neurological severity score was 6.1 (range 2 to 11). Significantly more severe ophthalmic manifestations were observed among older patients (p<0.005) and patients with more severe neurological findings (p<0.03). A direct correlation was found between the Ophthalmic Severity Scale and the Weill Cornell Neurological Scale (p<0.002). A direct association was also found between age and the ophthalmic manifestations (p<0.0002), with older children having more severe ophthalmic manifestations.

Conclusions: Ophthalmic manifestations of LINCL correlate closely with the degree of neurological function and the age of the patient. The newly established LINCL Ophthalmic Scale may serve as an objective marker of LINCL severity and disease progression, and may be valuable in the evaluation of novel therapeutic strategies for LINCL, including gene therapy.

Show MeSH

Related in: MedlinePlus

Weill Cornell LINCL Ophthalmic Severity Score 2.A. Dilated fundus photograph of Patient 10 reveals subtle pigmentary changes in the fovea (arrow). The optic nerve and vessels appearing normal. B. Late-phase FA and C. ICGA of Patient 17 shows a faint area of central hyper-fluorescence (arrow) surrounded by hypo-fluorescence. D. SD-OCT of patient 10 demonstrates normal retinal architecture outside the fovea (arrows). E. Enlargement of the fovea and para-foveal regions of the same OCT exposes outer retinal abnormalities including the disruption of the ellipsoid hyper-reflective band (*). The external limiting membrane, however, appears intact. FA – fluorescein angiogram, ICGA - indocyanine green angiogram, SD-OCT – spectral domain optical coherence tomography.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3756041&req=5

pone-0073128-g002: Weill Cornell LINCL Ophthalmic Severity Score 2.A. Dilated fundus photograph of Patient 10 reveals subtle pigmentary changes in the fovea (arrow). The optic nerve and vessels appearing normal. B. Late-phase FA and C. ICGA of Patient 17 shows a faint area of central hyper-fluorescence (arrow) surrounded by hypo-fluorescence. D. SD-OCT of patient 10 demonstrates normal retinal architecture outside the fovea (arrows). E. Enlargement of the fovea and para-foveal regions of the same OCT exposes outer retinal abnormalities including the disruption of the ellipsoid hyper-reflective band (*). The external limiting membrane, however, appears intact. FA – fluorescein angiogram, ICGA - indocyanine green angiogram, SD-OCT – spectral domain optical coherence tomography.

Mentions: There were no anterior segment abnormalities noted in any of the 50 eyes examined. All 50 eyes had white and quiet conjunctiva, a clear cornea, deep and quiet anterior chamber, flat iris, and clear lens. The vitreous cavity in all eyes appeared normal with an optically clear vitreous. Posterior segment findings ranged from a completely unremarkable dilated exam, OCT, FA, and ICGA to a severe, widespread retinal atrophy with complete absence of the outer retinal structures and the retinal pigment epithelium (RPE, Figures 1-5). The retinal degeneration was first noted in the macula, specifically in the parafoveal region, with subtle outer retinal and RPE abnormalities (Figure 2). These abnormalities then progressed from subtle pigmentary changes in the fovea (Figure 3) to a fulminant bull’s eye maculopathy, with a more widespread involvement of the outer retinal structures in the macula (Figure 4). In our series of LINCL patients, there was 100% correlation between the ophthalmic score in one eye and the ophthalmic score in the contralateral eye. The Supporting Information (Figure S1) shows representative images obtained on all 25 patients.


Spectrum of ocular manifestations in CLN2-associated batten (Jansky-Bielschowsky) disease correlate with advancing age and deteriorating neurological function.

Orlin A, Sondhi D, Witmer MT, Wessel MM, Mezey JG, Kaminsky SM, Hackett NR, Yohay K, Kosofsky B, Souweidane MM, Kaplitt MG, D'Amico DJ, Crystal RG, Kiss S - PLoS ONE (2013)

Weill Cornell LINCL Ophthalmic Severity Score 2.A. Dilated fundus photograph of Patient 10 reveals subtle pigmentary changes in the fovea (arrow). The optic nerve and vessels appearing normal. B. Late-phase FA and C. ICGA of Patient 17 shows a faint area of central hyper-fluorescence (arrow) surrounded by hypo-fluorescence. D. SD-OCT of patient 10 demonstrates normal retinal architecture outside the fovea (arrows). E. Enlargement of the fovea and para-foveal regions of the same OCT exposes outer retinal abnormalities including the disruption of the ellipsoid hyper-reflective band (*). The external limiting membrane, however, appears intact. FA – fluorescein angiogram, ICGA - indocyanine green angiogram, SD-OCT – spectral domain optical coherence tomography.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3756041&req=5

pone-0073128-g002: Weill Cornell LINCL Ophthalmic Severity Score 2.A. Dilated fundus photograph of Patient 10 reveals subtle pigmentary changes in the fovea (arrow). The optic nerve and vessels appearing normal. B. Late-phase FA and C. ICGA of Patient 17 shows a faint area of central hyper-fluorescence (arrow) surrounded by hypo-fluorescence. D. SD-OCT of patient 10 demonstrates normal retinal architecture outside the fovea (arrows). E. Enlargement of the fovea and para-foveal regions of the same OCT exposes outer retinal abnormalities including the disruption of the ellipsoid hyper-reflective band (*). The external limiting membrane, however, appears intact. FA – fluorescein angiogram, ICGA - indocyanine green angiogram, SD-OCT – spectral domain optical coherence tomography.
Mentions: There were no anterior segment abnormalities noted in any of the 50 eyes examined. All 50 eyes had white and quiet conjunctiva, a clear cornea, deep and quiet anterior chamber, flat iris, and clear lens. The vitreous cavity in all eyes appeared normal with an optically clear vitreous. Posterior segment findings ranged from a completely unremarkable dilated exam, OCT, FA, and ICGA to a severe, widespread retinal atrophy with complete absence of the outer retinal structures and the retinal pigment epithelium (RPE, Figures 1-5). The retinal degeneration was first noted in the macula, specifically in the parafoveal region, with subtle outer retinal and RPE abnormalities (Figure 2). These abnormalities then progressed from subtle pigmentary changes in the fovea (Figure 3) to a fulminant bull’s eye maculopathy, with a more widespread involvement of the outer retinal structures in the macula (Figure 4). In our series of LINCL patients, there was 100% correlation between the ophthalmic score in one eye and the ophthalmic score in the contralateral eye. The Supporting Information (Figure S1) shows representative images obtained on all 25 patients.

Bottom Line: Significantly more severe ophthalmic manifestations were observed among older patients (p<0.005) and patients with more severe neurological findings (p<0.03).A direct correlation was found between the Ophthalmic Severity Scale and the Weill Cornell Neurological Scale (p<0.002).A direct association was also found between age and the ophthalmic manifestations (p<0.0002), with older children having more severe ophthalmic manifestations.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Weill Cornell Medical College, New York, New York, United States of America.

ABSTRACT

Background: Late infantile neuronal ceroid lipofuscinosis (LINCL), one form of Batten's disease is a progressive neurodegenerative disorder resulting from a CLN2 gene mutation. The spectrum of ophthalmic manifestations of LINCL and the relationship with neurological function has not been previously described.

Methods: Patients underwent ophthalmic evaluations, including anterior segment and dilated exams, optical coherence tomography, fluorescein and indocyanine green angiography. Patients were also assessed with the LINCL Neurological Severity Scale. Ophthalmic findings were categorized into one of five severity scores, and the association of the extent of ocular disease with neurological function was assessed.

Results: Fifty eyes of 25 patients were included. The mean age at the time of exam was 4.9 years (range 2.5 to 8.1). The mean ophthalmic severity score was 2.6 (range 1 to 5). The mean neurological severity score was 6.1 (range 2 to 11). Significantly more severe ophthalmic manifestations were observed among older patients (p<0.005) and patients with more severe neurological findings (p<0.03). A direct correlation was found between the Ophthalmic Severity Scale and the Weill Cornell Neurological Scale (p<0.002). A direct association was also found between age and the ophthalmic manifestations (p<0.0002), with older children having more severe ophthalmic manifestations.

Conclusions: Ophthalmic manifestations of LINCL correlate closely with the degree of neurological function and the age of the patient. The newly established LINCL Ophthalmic Scale may serve as an objective marker of LINCL severity and disease progression, and may be valuable in the evaluation of novel therapeutic strategies for LINCL, including gene therapy.

Show MeSH
Related in: MedlinePlus