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Microperimetric biofeedback in a patient with oculocutaneous albinism

2013; Elsevier BV; Volume: 48; Issue: 5 Linguagem: Inglês

10.1016/j.jcjo.2012.11.011

1715-3360

Pier Luigi Grenga, Paolo Trabucco, Alessandro Meduri, Serena Fragiotta, Enzo Maria Vingolo,

Biochemical Analysis and Sensing Techniques

Oculocutaneous albinism (OCA) is a rare autosomal recessive inherited disorder, part of a heterogeneous group of genetic conditions that occur in autosomal recessive manner characterized by a complete or partial absence of pigment in the skin, hair, or eyes, caused by an alteration of the production of melanin pigment in the biosynthetic process of tyrosinase enzyme.1Gronskov K. Ek J. Brondum-Nielsen K. Oculocutaneous albinism.Orphanet J Rare Dis. 2007; 2: 43Crossref PubMed Scopus (329) Google Scholar In OCA hair, skin, and eyes are involved; in ocular albinism (OA), only eyes are involved. Although various forms are present, the alterations in the eye are common to all of these and are probably due to the reduction of melanin during embryonic development and early postnatal life. Typically, in these individuals is present a decreased visual acuity, nystagmus, strabismus, and refractive errors. Examination of anterior segment reveals a hypopigmentation of the iris; this lack of pigment involves also the retina and a foveal hypoplasia is present, probably because of an arrest of development.2Gargiulo A. Testa F. Rossi S. et al.Molecular and clinical characterization of Albinism in a large cohort of Italian Patients.Inv Ophthalmol Vis Sci. 2011; 52: 1281-1289Crossref PubMed Scopus (49) Google Scholar, 3McAllister J.T. Dubis A.M. Diane M.T. et al.Arrested development: high-resolution imaging of foveal morphology in albinism.Vis Res. 2010; 50: 810-817Crossref PubMed Scopus (98) Google ScholarVarious techniques of biofeedback, such as plain light stimulus, acoustic biofeedback, and structured light stimulus plus acoustic biofeedback have been applied to congenital nystagmus, amblyopia, and macular disease, and have proved to be efficacious in the improvement of visual function in these disorders.4Contestabile M.T. Recupero S.M. Palladino D. et al.A new method of biofeedback in the management of low vision.Eye. 2002; 16: 472-480Crossref PubMed Scopus (24) Google Scholar, 5Vingolo E.M. Cavarretta S. Domanico D. et al.Microperimetric biofeedback in AMD patients.Appl Psychophysiol Biofeedback. 2007; 32: 185-189Crossref PubMed Scopus (53) Google Scholar, 6Mezawa M. Ishikawa S. Ukai K. Changes in waveform of congenital nystagmus associated with biofeedback treatment.Br J Ophthalmol. 1990; 74: 472-476Crossref PubMed Scopus (35) Google Scholar, 7Vingolo E.M. Salvatore S. Cavarretta S. Low-vision rehabilitation by means of MP-1 biofeedback examination in patients with different macular diseases: a pilot study.Appl Psychophysiol Biofeedback. 2009; 34: 127-133Crossref PubMed Scopus (53) Google Scholar, 8Nilsson U.L. Frennesson C. Nilsson S.E. Patients with AMD and a large absolute central scotoma can be trained successfully to use eccentric viewing, as demonstrated in a scanning laser ophthalmoscope.Vis. Res. 2003; 43: 1777-1787Crossref PubMed Scopus (175) Google ScholarThe purpose of this study was to estimate the benefits of low-vision rehabilitation using microperimetric (MP-1, software version 1.7.6; Nidek Technologies) biofeedback examination to increase the stability of fixation in a young patient with OCA.A 14-year-old female with OCA was referred in 2011 at our retinal disease unit; her ocular history was positive for nystagmus and hyperopia. Systemic and family history was positive for a 6-year-old brother with OCA; her parents were negative for OCA and OA. Her BCVA was 20/50 in RE and 20/40 in LE; she had nystagmus and strabismus. Anterior segment examination showed light blue iris pigmentation and high degree of iris translucency in both eyes (grade 3); fundus examination revealed in both eyes mild degree of fundus hypopigmentation (grade 2). A 4- and 3-point scale according to Summers et al.9Summers C.G. Knobloch W.H. Witkop Jr, C.J. King R.A. Hermansky Pudlak syndrome. Ophthalmic findings.Ophthalmology. 1988; 95: 545-554Abstract Full Text PDF PubMed Scopus (92) Google Scholar was used to classify iris translucency and macular transparency, respectively. Multiple single scans of the macula, each composed of 50 averaged frames and passing through the fovea, were acquired using the Heidelberg Spectralis spectral-domain optical coherence tomography. Those images showed in both eyes absence of foveal pit (Fig. 1).MP-1 tests were performed in a darkened room, and pupils were dilated with 1 drop each of tropicamide 1% and phenylephrine 2.5%. A red cross of 2 degrees was used as the fixation target, monochromatic white background illumination set to 4 apostilbs (1.27 cd/m2), stimulus size set to Goldmann III with a projection time of 200 msec, and customized grid of 68 stimuli around 10 degrees centered on the “putative” fovea. A 4-2-1 staircase strategy was used, and the first stimulus was fixed at 16 dB. Results about retinal sensitivity were reported in decibels. Fixation stability was quantified by calculating a bivariate contour ellipse area (BCEA) encompassing 68% of fixations points (first standard deviation). This measure is based on the values of the standard deviations of the horizontal and vertical eye movements during fixation, and the correlation coefficient (Pearson product-moment correlation coefficient) of the horizontal and vertical eye positions. BCEA was calculated using the formula previously reported by Timberlake et al.10Timberlake G.T. Sharma M.K. Grose S.A. et al.Retinal location of the preferred retinal locus relative to the fovea in scanning laser ophthalmoscope images.Optom Vis Sci. 2005; 82: 177-185Crossref PubMed Google Scholar The follow-up protocol was used to repeat the examination: the operator manually selects two high-contrast landmarks on the infrared images; then the software automatically detects the same landmarks in the second infrared image. The low-vision rehabilitation consisted of 10 training sessions of 10 minutes for each eye, performed once a week using the MP-1 biofeedback examination. The patient was asked to move her eyes according to an audiofeedback that advised her whether she was getting closer to the desired final fixation position. A written informed consent was obtained from the patient and her parents.At baseline, mean retinal sensitivity was 19.3 dB in the RE and 19.5 dB in the LE; BCEA was 2.13 deg2 in the RE and 1.68 deg2 in the LE. After 5 weeks of biofeedback training, mean retinal sensitivity was 19.8 dB in the RE and 19.7 dB in the LE, whereas BCEA was 1.50 deg2 in the RE and 1.49 deg2 in the LE. After 10 weeks of training, mean retinal sensitivity was 19.2 dB in the RE and 17.9 dB in the LE; BCEA was 0.73 deg2 in the RE and 0.63 deg2 in the LE. There was not a statistically significant difference in mean retinal sensitivity between baseline, 5 weeks, and 10 weeks after training (paired t test, p = 0.25, p = 0.46, p = 0.29, respectively). There was a statistically significant difference in BCEA between 5 and 10 weeks after training (paired t test, p = 0.03; Fig. 2). BCVA at 5 and 10 weeks did not change when compared with baseline.Fig. 2Microperimetry (MP-1) images showing retinal sensitivity map and bivariate contour ellipse area at each follow-up. LE, left eye; RE, right eye.View Large Image Figure ViewerDownload (PPT)Our results showed that after microperimetric biofeedback, there is a significant improvement in fixation stability in both eyes, with reduction of the horizontal eye movement and, consequently, of the fixation area calculated by means of BCEA. Even if our case report demonstrates a consistent improvement of fixation stability, this is not associated with an increase in functional responses such as BCVA and mean retinal sensitivity, and it could not imply a consistent change in disease-related damage. Furthermore, microperimetric biofeedback therapy is a simple and low-cost therapy that does not affect the quality of life of these patients and has an extremely low rate of complications.Mezawa et al.6Mezawa M. Ishikawa S. Ukai K. Changes in waveform of congenital nystagmus associated with biofeedback treatment.Br J Ophthalmol. 1990; 74: 472-476Crossref PubMed Scopus (35) Google Scholar have described an improvement in fixation stability after acoustic biofeedback in patients with nystagmus, but they excluded patients with OA or partial variant of it. Currently, there are no evidences in the literature for the microperimetric biofeedback in patients with OCA or foveal hypoplasia. Further studies are required to evaluate the influence of microperimetric biofeedback in a large cohort of patients with OCA, foveal hypoplasia, and nystagmus, and to establish the real effectiveness of the fixation stability improvement when correlated with reading speed. Oculocutaneous albinism (OCA) is a rare autosomal recessive inherited disorder, part of a heterogeneous group of genetic conditions that occur in autosomal recessive manner characterized by a complete or partial absence of pigment in the skin, hair, or eyes, caused by an alteration of the production of melanin pigment in the biosynthetic process of tyrosinase enzyme.1Gronskov K. Ek J. Brondum-Nielsen K. Oculocutaneous albinism.Orphanet J Rare Dis. 2007; 2: 43Crossref PubMed Scopus (329) Google Scholar In OCA hair, skin, and eyes are involved; in ocular albinism (OA), only eyes are involved. Although various forms are present, the alterations in the eye are common to all of these and are probably due to the reduction of melanin during embryonic development and early postnatal life. Typically, in these individuals is present a decreased visual acuity, nystagmus, strabismus, and refractive errors. Examination of anterior segment reveals a hypopigmentation of the iris; this lack of pigment involves also the retina and a foveal hypoplasia is present, probably because of an arrest of development.2Gargiulo A. Testa F. Rossi S. et al.Molecular and clinical characterization of Albinism in a large cohort of Italian Patients.Inv Ophthalmol Vis Sci. 2011; 52: 1281-1289Crossref PubMed Scopus (49) Google Scholar, 3McAllister J.T. Dubis A.M. Diane M.T. et al.Arrested development: high-resolution imaging of foveal morphology in albinism.Vis Res. 2010; 50: 810-817Crossref PubMed Scopus (98) Google Scholar Various techniques of biofeedback, such as plain light stimulus, acoustic biofeedback, and structured light stimulus plus acoustic biofeedback have been applied to congenital nystagmus, amblyopia, and macular disease, and have proved to be efficacious in the improvement of visual function in these disorders.4Contestabile M.T. Recupero S.M. Palladino D. et al.A new method of biofeedback in the management of low vision.Eye. 2002; 16: 472-480Crossref PubMed Scopus (24) Google Scholar, 5Vingolo E.M. Cavarretta S. Domanico D. et al.Microperimetric biofeedback in AMD patients.Appl Psychophysiol Biofeedback. 2007; 32: 185-189Crossref PubMed Scopus (53) Google Scholar, 6Mezawa M. Ishikawa S. Ukai K. Changes in waveform of congenital nystagmus associated with biofeedback treatment.Br J Ophthalmol. 1990; 74: 472-476Crossref PubMed Scopus (35) Google Scholar, 7Vingolo E.M. Salvatore S. Cavarretta S. Low-vision rehabilitation by means of MP-1 biofeedback examination in patients with different macular diseases: a pilot study.Appl Psychophysiol Biofeedback. 2009; 34: 127-133Crossref PubMed Scopus (53) Google Scholar, 8Nilsson U.L. Frennesson C. Nilsson S.E. Patients with AMD and a large absolute central scotoma can be trained successfully to use eccentric viewing, as demonstrated in a scanning laser ophthalmoscope.Vis. Res. 2003; 43: 1777-1787Crossref PubMed Scopus (175) Google Scholar The purpose of this study was to estimate the benefits of low-vision rehabilitation using microperimetric (MP-1, software version 1.7.6; Nidek Technologies) biofeedback examination to increase the stability of fixation in a young patient with OCA. A 14-year-old female with OCA was referred in 2011 at our retinal disease unit; her ocular history was positive for nystagmus and hyperopia. Systemic and family history was positive for a 6-year-old brother with OCA; her parents were negative for OCA and OA. Her BCVA was 20/50 in RE and 20/40 in LE; she had nystagmus and strabismus. Anterior segment examination showed light blue iris pigmentation and high degree of iris translucency in both eyes (grade 3); fundus examination revealed in both eyes mild degree of fundus hypopigmentation (grade 2). A 4- and 3-point scale according to Summers et al.9Summers C.G. Knobloch W.H. Witkop Jr, C.J. King R.A. Hermansky Pudlak syndrome. Ophthalmic findings.Ophthalmology. 1988; 95: 545-554Abstract Full Text PDF PubMed Scopus (92) Google Scholar was used to classify iris translucency and macular transparency, respectively. Multiple single scans of the macula, each composed of 50 averaged frames and passing through the fovea, were acquired using the Heidelberg Spectralis spectral-domain optical coherence tomography. Those images showed in both eyes absence of foveal pit (Fig. 1). MP-1 tests were performed in a darkened room, and pupils were dilated with 1 drop each of tropicamide 1% and phenylephrine 2.5%. A red cross of 2 degrees was used as the fixation target, monochromatic white background illumination set to 4 apostilbs (1.27 cd/m2), stimulus size set to Goldmann III with a projection time of 200 msec, and customized grid of 68 stimuli around 10 degrees centered on the “putative” fovea. A 4-2-1 staircase strategy was used, and the first stimulus was fixed at 16 dB. Results about retinal sensitivity were reported in decibels. Fixation stability was quantified by calculating a bivariate contour ellipse area (BCEA) encompassing 68% of fixations points (first standard deviation). This measure is based on the values of the standard deviations of the horizontal and vertical eye movements during fixation, and the correlation coefficient (Pearson product-moment correlation coefficient) of the horizontal and vertical eye positions. BCEA was calculated using the formula previously reported by Timberlake et al.10Timberlake G.T. Sharma M.K. Grose S.A. et al.Retinal location of the preferred retinal locus relative to the fovea in scanning laser ophthalmoscope images.Optom Vis Sci. 2005; 82: 177-185Crossref PubMed Google Scholar The follow-up protocol was used to repeat the examination: the operator manually selects two high-contrast landmarks on the infrared images; then the software automatically detects the same landmarks in the second infrared image. The low-vision rehabilitation consisted of 10 training sessions of 10 minutes for each eye, performed once a week using the MP-1 biofeedback examination. The patient was asked to move her eyes according to an audiofeedback that advised her whether she was getting closer to the desired final fixation position. A written informed consent was obtained from the patient and her parents. At baseline, mean retinal sensitivity was 19.3 dB in the RE and 19.5 dB in the LE; BCEA was 2.13 deg2 in the RE and 1.68 deg2 in the LE. After 5 weeks of biofeedback training, mean retinal sensitivity was 19.8 dB in the RE and 19.7 dB in the LE, whereas BCEA was 1.50 deg2 in the RE and 1.49 deg2 in the LE. After 10 weeks of training, mean retinal sensitivity was 19.2 dB in the RE and 17.9 dB in the LE; BCEA was 0.73 deg2 in the RE and 0.63 deg2 in the LE. There was not a statistically significant difference in mean retinal sensitivity between baseline, 5 weeks, and 10 weeks after training (paired t test, p = 0.25, p = 0.46, p = 0.29, respectively). There was a statistically significant difference in BCEA between 5 and 10 weeks after training (paired t test, p = 0.03; Fig. 2). BCVA at 5 and 10 weeks did not change when compared with baseline. Our results showed that after microperimetric biofeedback, there is a significant improvement in fixation stability in both eyes, with reduction of the horizontal eye movement and, consequently, of the fixation area calculated by means of BCEA. Even if our case report demonstrates a consistent improvement of fixation stability, this is not associated with an increase in functional responses such as BCVA and mean retinal sensitivity, and it could not imply a consistent change in disease-related damage. Furthermore, microperimetric biofeedback therapy is a simple and low-cost therapy that does not affect the quality of life of these patients and has an extremely low rate of complications. Mezawa et al.6Mezawa M. Ishikawa S. Ukai K. Changes in waveform of congenital nystagmus associated with biofeedback treatment.Br J Ophthalmol. 1990; 74: 472-476Crossref PubMed Scopus (35) Google Scholar have described an improvement in fixation stability after acoustic biofeedback in patients with nystagmus, but they excluded patients with OA or partial variant of it. Currently, there are no evidences in the literature for the microperimetric biofeedback in patients with OCA or foveal hypoplasia. Further studies are required to evaluate the influence of microperimetric biofeedback in a large cohort of patients with OCA, foveal hypoplasia, and nystagmus, and to establish the real effectiveness of the fixation stability improvement when correlated with reading speed.