Sapienza, University of Rome Facciolo G, Gagliardi A, Vingolo E.M. Glaucoma: biofeedback strategies withMicroperimetry
_______________________ Corresponding Author: Giuliana Facciolo Email: juliana9@hotmail.it
Purpose: Low vision rehabilitation in advanced optic nerve damage was described previously in several reports demonstrating its positive effect in improving visual performances. Initially proposed simply as magnification system(optical and optoelectronics), in actual clinical practice new diagnostic and informatic tools helped the patient as active tasks for visual function recovery. Microperimetry allows to follow up the progression of the disease, to exactly localize position shape and deepness of the scotoma and finally tohave a precise localization and evaluation of fixation. The goal of our study is to assess in a selected population of advanced glaucoma patients if microperimetric biofeedback may be able to restore partially some visual tasks. Materials: Were selected 10 patients (18 eyes) with advanced primary open angle glaucoma that underwent to a rehabilitative protocol as follows: visual acuity evaluation, reading speed, microperimetry, fixation analysis (BCEA or Bivariate Contour Ellipse Area). Each patient scheduled 10 sessions of biofeedback for eye (10 minute each), recall of biofeedback schedulinowas reproposed at month 4-8-12. Statistical analysis was performed with double tailed T test student and Spearman to correlate reading speed and visual acuity with retinal sensitivity. Results: Mean visual acuity at baseline was 0.98 ± 0,66logMAR and at the end of scheduled protocol was 0,75 ± 0,60 logMAR; this value was statistically significant (p>0.05); reading speed was 31,4 ± 4,3 w/m at baseline and 55,6 ± 3,2 w/m at the end of training (p<0.05). Conclusions: Biofeedback rehabilitative strategy was certainly useful for advanced glaucoma patients in terms of visual acuity and retinal sensitivity; it causes a very impressive change in visual expectance of the patients determining a better quality of life.
INTRODUCTION Glaucoma is a chronic degenerative disease in which main clinical signs areoptic nerve head damage with visual field alterations and high intraocular pressure. In late stage, when central portion of visual field has damaged, clinician looses one of the main parameters to evaluate disease progression and the patient experiences a very heavy loss in visual function that determines a limitation in common tasks and daily activities. In our study, we attempt to reduce the impact of visual field alterations in patients with late phase glaucoma, with the goal of reducing visual difficulties, by the mean of newly designed biofeedback strategies withMAIA microperimeter(Centervue, Padua â&#x20AC;&#x201C; Italy). This technique, presenting luminous stimulus, allows us to train fixation tasks, if necessary, or to select a new Preferential Retinal Location (PRL) in patients with loss of central fixation.Acoustic feedback indicates to the patient if Target Retinal Location (TRL) and fixation stability has reached. Biofeedback technique gives patient the knowledge of his fixation location and the frequency of sound indicates how far from the target zone is patient looking. In this study were evaluated best corrected visual acuity (BCVA), reading speed, fixation stability and localization with particular regard to the Behaviour Contour Ellipse Area (BCEA). The aim of the study is to evaluate if, scheduling repeated sessions of microperimetric biofeedback, with MAIA, we may be able to improve visual performances of late stage glaucoma patients to obtain better quality of sight.
MATERIALS &METHODS Were selected 10 patients affected bylate stage primary open: 7male and 3 femalemean age 65,12years (between 59 and 71 yrs), a total of18 eyes were examined, enrolled in UOC OculisticaUniversitaria in the “A. Fiorini”HospitalTerracina Italy. Inclusioncriteria were: ageincluded between 40 and 75 years,glaucoma diagnosisat least 10 years before the visit, cup disk ratio high than 0.7 or asymmetry between eyes higher than 0.2, instruction level at least high school. Exclusioncriteria wereprimary glaucoma narrow angle, previously performed vitreoretinal surgical intervention, eye disease cornea, uveitis, vitreo-retinial diseases. All patients underwent tobiomicroscopic examination ofanteriorand posteriorsegment, visual acuity evaluation, Goldmannapplanationtonometry, gonioscopy(Goldmannlens), automatedcomputerized perimetry(HumpreyHFA) threshold test 30-2, Optical Coherence Tomography (Heidelberg HRA, TMB module; Heidelberg-Germania) to evaluate retinal and RFNL layer thickness.Visual acuity in the worse eye was at baseline lower than 20/200, MD higher than -24 DB.At baseline was measured BCVA, for near and distance, data were evaluated as logMAR for statistical purpose. Near visual acuity was measured in CP on a randomized computerized text black on white mean difficulty for a common reader in italian, MN-Read text in Italian was chosen for reading speed measurements. Each eye was tested singularly. Microperimetry tested single point retinal sensitivity with MAIA microperimeter(CenterVue, Padua, Italia), 10-2 automaticprogram, 4-2 threshold strategyfixation point was single 1°. For highly impaired patients, which were not able to perceive this dimension, we increased progressively size (2°) and thickness. Goldmann III size white test on a white background was used, intensity variedfrom 0 dB and 36 dB, presentation time was 200 ms.On same Microperimetry we automatically evaluated fixation according Fujii classification and BCEA surface expressed in square degree to obtain a quite-normal distribution of values. Rehabilitativeprotocol was scheduled as follows: session lasts 20 min once a week, for 10 weeks, Biofeedback training sessions were performed withMAIA microperimeter. These sessions were repeated at 4, 8 and 12months. Duringeach session, first step was fixation training towardfoveal reflex with an acoustic feedback that allows to the patient knowing how they are looking; if fixation was efficient the sound was high, while when the gaze was far from the fixation point the sound became discontinuous and weaker: each session was monitored on line. At the end of rehabilitative protocol (12 months) all patientswere examined again: far and near BCVA, reading speed, microperimetry andfixation examination. Microperimetry was performed with follow-up strategy, in which each point was tested exactly in the same position and in the same illumination conditions of the previous examination (obtained through ROI localization on the retina). Statisticalanalysiswas performed with double tailed t-test Student, values p<0,05were considered statistically significant. Spearman correlation was used to relate retinal sensitivity to BCVA and reading speed.
RESULTS All patients completed the scheduled rehabilitative protocol. After that 13 eyes (72,22%) on 18 showed an improvement. Mean BCVA at baseline was 0.98 ± 0,66logMARat the end was 0,75 ± 0,60 logMAR (p=0,32, not statistically significant). Reading speed statistically progressed from a mean value of 31,4 ± 4,3 words/minute at baseline to 55,6 ± 3,2 w/min at the end of training (p=0,031). Also meanretinalsensitivityimproved from 7,43 ± 8,28 dB to 8,33 ± 9,04 dB this values were statistically significant (p=0,022). Fixation evaluation showed improvement both in terms of stability andin localization.Fuji meanvalues were P1=27% P2=77% at baseline and at P1=77% P2=93% after 12 months (p<0,05); these values were statistically significant.BCEA calculation presented a reduction in shape and size in a statistically significant wayfrom 63% = 9,6 deg2; and 95% = 34,13 deg2to63% =4,03 deg2 ;and 95% = 17,03 deg2( p < 0,05). Spearman correlation showed positiverelationships between single point retinal sensitivity and visual acuity and reading speed (r=0,58).
1. Above, on the left: sensitivity map before the training; on the right: sensitivity map after the training. It can beobserved an improvement of retinal sensitivity as well as fixation behavior after the visual rehabilitation( Below. Before: instable F.: P1:29%, P2:71%; after:relatively unstable F.: P1:70%, P2:88% ).
DISCUSSION Glaucoma is one of main causes of acquired blindness worldwide49. It is an asymptomatic disease especially in the early stage of its onset. Visual field deficit departs from the blind spot as Bjerrum scotoma and at a late phase of the disease resulting in a concentric reduction with foveal diminution in retinal sensitivity, which is so deep to determine functional damage that hampers common daily activities of the patient and to limit his autonomy10. In our study, conductedon late stage glaucoma, patientstested biofeedback visual rehabilitationperformed by MAIA strategy. The study population presented a statistically significant improvement of visual performances at the end of the rehabilitative protocol. Namely in reading speed and fixation stability,it was demonstrated the reduction of BCEA, meaning that fixationsaccades oscillation was concentrated after the training. Inclinical practice,biofeedback training stabilizes, duringseveral sessions, the PRL that becomes TRL, which is the new area of retina more useful to be finalized in better vision4,17,18. Our used standard procedure, overlapping fundus images, allowed to choose better function area clearly stressed out by the fixation cloud; this area must contains at least four consecutive letters to have a good reading speed (preferably localized in the upper retina and horizontally as near as possible to the fovea)44. As a consequence of biofeedback training andstimulation,new TRL determines improvement in near visual acuity e reading speed11,12. These results confirmthe utility of this technology in late stage of glaucoma. This system takes in advantage cerebral plasticity, passing towards a remodeling of ganglion cell synapses2. Moreover,neurosensorial adaptive tasks allow to override the lesions utilizing horizontal connections departed from other retinal eccentric regions; at the same time,the start of new fixation strategies overlaythe optic nerve lesion, with the aim to obtain an improvement in visual abilities2,14. It is clear thatvisual rehabilitation is not only an intraocular rearrangement, but also involves brainâ&#x20AC;&#x2122;s upper level of neurosensorialconnections. For a long time, visual loss caused by retinal lesions or by cerebral damagewas considered not reversible. Nevertheless, more studies on animals and humans in last ten years, demonstrated that there is a very high plasticity in the neural system that remains also in older patients.According to â&#x20AC;&#x153;neurosinaptic plasticitytheoryâ&#x20AC;?, it is possible to stimulate formation of new synapses improving neurofunctional and neurovisual performancestowards retinal or cortical training performed by different devices. In this way, via horizontal or amacryne cells would be possible to stimulate areas near to the lost fovea having better visual outcomes41,42,56. In glaucoma patients, visual training determines better functioning and recruitment of undamaged areas leading to recovery of sharpness, contrast sensitivity and faster lock-in timein the visual saccades, either near damaged fibers or in immediately surrounding areas40,46,47,48. Recent studyconducted onglaucoma patients demonstrated that visual loss, even in advanced glaucoma, may be not permanent but it could be possible to reverse the retinal cortical transmissionvia surviving ganglion cells situated in deeper retinal or cortical areas.
Iterative and repetitive stimulation are able to speed up intra fibers bioelectrical transmission requiring different scheduling depending from visual resources.Several studies are still required to investigate visual recovery in these clinical conditions with EEG and MRI31,53. Nevertheless positive results obtained in several studies, individual capabilities to maintain visual performance are still a chimera because most of the patients loose the achieved better performances after few months (4-6), so that recalling sessions need to be scheduled regularly to have a stable visual performance. Finally, in this study microperimetry prove to be a good technical device.Eye-tracker allows a precise rendering of fixation spots, so that it is very easy to train a new PRL obtaining good functional results. More than 70% of patients showed an improvement of functional visual tasks and they noted a real improvement in their quality of vision.
REFERENCES
1. AAnastasakis, JJ McAnany, GA Fishman and WH Seiple. Clinical value, normative retinal sensitivity values, and intrasession repeatability using a combined spectral domain optical coherence tomography/ scanning laser ophthalmoscope microperimeter. 2. Andrade MA, Muro EM, Morรกn F (2001). Simulation of plasticity in the adult visual cortex. BiolCybern 84:445-451. 3. Angelica Cerulli, Massimo Cesareo, Elena Ciuffoletti, Maria Lucia Montanaro, Raffaele Mancino, Concetta Mirisola, Roberto Sorge, Claudio Cedrone, Carlo Nucci, Luciano Cerulli. Evaluation of eye movements pattern during reading process in patients with galucoma: a microperimeter study. 4. Angi MR, Caucci S, Pilotto E, et al (1996). Changes in myopia, visual acuity, and psychological distress after biofeedback visual training. Optom Vis Sci 73:35-42. 5. Bernhard A. Sabel, PhD1; Julia Gudlin, PhD Institute of Medical Psychology, Medical Faculty, Otto-von-Guericke University of Magdeburg, Magdeburg, Germany. Vision Restoration Training for Glaucoma: A Randomized Clinical Trial. 6. Bourne RR (2006). Worldwide glaucoma through the looking glass. Br J Ophthalmol 90:253-254. 7. Buia C, Tiesinga P (2006). Attentional modulation of firing rate and synchrony in a model cortical network. J ComputNeurosci 20:247-264. 8. Cannata R, Salvatore S, Girolami I, et al (2009). Acoustic biofeedback training in high myopic eyes. ARVO 2009 Annual Meeting 3-7 May Fort Lauderdale, Florida. 9. Carpineto P, Ciancaglini M, Di Antonio L, et al (2007). Fundus microperimetry patterns of fixation in type 2 diabetic patients with diffuse macular edema. Retina 27:21-29. 10. Casson RJ, Chidlow G, Wood JP, et al (2012). Definition of glaucoma: clinical and experimental concepts. Clin Experiment Ophthalmol 40:341-349. 11. Contestabile MT, Recupero SM, Palladino D, et al (2002). A new method of biofeedback in the management of low vision. Eye (Lond) 16:472-480. 12. Crossland MD, Culham LE, Kabanarou SA, et al (2005). Preferred retinal locus development in patients with macular disease. Ophthalmology 112:1579-1585. 13. Crossland MD, Dunbar HM, Rubin GS (2009). Fixation stability measurement using the MP1 microperimeter. Retina29:651-656.
14. D’Angelo E (2012). New trends in neuroscience: the challenge of functional neurology. FunctNeurol 27:5. 15. Donald C. Fletcher, Manfred MacKeben. MICROPERIMETRY CORRESPONDENCE Everyday use of modern microperimetry in a low-vision service. 16. EdoardoMidena, MD, Stela Vujosevic, MD, Fabiano Cavarzeran, ScD, for the Microperimetry Study Group. Normal Values for Fundus Perimetry with the Microperimeter MP1. 17. Eric Halperin, Robert L. Yolton. Ophthalmic Applications of Biofeedback. 18. Francesca Verboschi, MD, Daniela Domanico, MD, Marcella Nebbioso, MD,Giulia Corradetti, MD, Sergio Zaccaria Scalinci, MD Enzo Maria Vingolo, MD, PhD. New trends in visual rehabilitation with MP-1microperimeter biofeedback: optic neural dysfunction. 19. Fujii GY, de Juan E Jr, Sunness J, et al (2002). Patient selection for macular translocation surgery using the scanning laser ophthalmoscope. Ophthalmology 109:1737-1744. 20. Giorgi D, Contestabile MT, Pacella E, et al (2005). An instrument for biofeedback applied to vision. ApplPsychophysiol Biofeedback 30:389-395. 21. Gupta N, Ang LC, Noël de Tilly L, et al (2006). Human glaucoma and neural degeneration in intracranial optic nerve, lateral geniculate nucleus, and visual cortex. Br J Ophthalmol 90:674-678. 22. Kasten E, Sabel BA (1995). Visual field enlargement after computer training in braindamaged patients with homonymous deficits: an open pilot trial. RestorNeurolNeurosci 8:113-127. 23. Kasten E, Wüst S, Behrens-Baumann W, et al (1998). Computer-based training for the treatment of partial blindness. Nat Med 4:1083-1087. 24. Kirby E, Bandelow S, Hogervorst E (2010). Visual impairment in Alzheimer's disease: a critical review. J Alzheimers Dis 21:15-34. Leung V, Wick B, Bedell HE (1996). Multifaceted treatment of congenital nystagmus: a report of 6 cases. Optom Vis Sci 73:114124. 25. Klaus Rohrschneider, MD, Christina Springer, MD, StefanBultmann, MD And Hans E. Volcker, MD. Microperimetry — Comparison Between the Micro Perimeter 1 and Scanning Laser Ophthalmoscope — Fundus Perimetry. 26. Mangione CM, Lee PP, Gutierrez PR, et al (2001). Development of the 25-item National Eye Institute Visual Function Questionnaire. rchOphthalmol 119:1050-1058. 27. MarikaUrbanski, Olivier A. Coubard, and ClémenceBourlon. Visualizing the blind brain: brain imaging of visual field defects from early recovery to rehabilitation techniques. 28. Mezawa M, Ishikawa S, Ukai K (1990). Changes in waveform of congenital nystagmus associated with biofeedback treatment. Br J Ophthalmol 74:472-476. 29. Midena E1. Microperimetry. Arch SOC ESP OFTALMOL 2006; 81: 183-186. 30. Monica Varano, MD. Up-to-date: microperimetria e applicazioni nella gestione delle patologie maculari. 31. Nebbioso M, De Gregorio F, Prencipe L, et al (2011). Psychophysical and electrophysiological testing in ocular hypertension. Optom Vis Sci 88:E928-939. 32. Nitin Nigam, MD, Dirk-Uwe G. Bartsch, PHD, Lingyun Cheng, MD, ManpreetBrar, MD, Ritchie M. S. Yuson, MD, Igor Kozak, MD, Francesca Mojana, MD, William R. Freeman, MD. Spectral domain optical coherence tomography for imaging ERM, retinal edema, and vitreomacular interface. 33. Noboru Shima, MD; Samuel N. Markowitz, MD, FRCSC; Sophia V. Reyes, MD. Concept of a functional retinal locus in age-related macular degeneration. 34. Pacella E, Pacella F, Mazzeo F, et al (2012). Effectiveness of vision rehabilitation treatment through MP-1 microperimeter in patients with visual loss due to macular disease. ClinTer 163:e423-428.
35. Pache M, Flammer J (2006). A sick eye in a sick body? Systemic findings in patients with primary open-angle glaucoma. SurvOphthalmol 51:179-212. 36. Prokofyeva E, Zrenner E (2012) Epidemiology of major eye disease leading to blindness in Europe: a literature review. Ophthalmic Research 47: 171-188. 37. Resnikoff S, Pascolini D, Etyaâ&#x20AC;&#x2122;ale D, et al (2004). Global data on visual impairment in the year 2002. Bull World Health Organ 82:844-851. 38. Romano JG, Schulz P, Kenkel S, et al (2008). Visual field changes after a rehabilitation intervention: vision restoration therapy. J NeurolSci 273:70-74. 39. Rupolo G, Angi M, Sabbadin E, et al (1997). Treating myopia with acoustic biofeedback: a prospective study on the evolution of visual acuity and psychological distress.Psychosom Med 59:313-317. 40. S. Miglior. Microperimetry and glaucoma. 41. Sabel BA, Henrich-Noack P, Fedorov A, et al (2011). Vision restoration after brain and retina damage: the "residual vision activation theory". Prog Brain Res 192:199-262. 42. SafranAB,Landis T (1996). Plasticity in the adult visual cortex: implications for the diagnosis of visual field defects and visual rehabilitation. CurrOpinOphthalmol 7:53-64. 43. Samuel N. Markowitz, MD, FRCS(C). Microperimeters and micro- perimetry: new technology in ophthalmology with far-reaching applications. 44. Samuel N. Markowitz, MD, FRCSC, Sophia V. Reyes, MD. Microperimetry and clinical practice: an evidence-based review. 45. Serena Salvatore, Aloisa Librando, Mariacristina Esposito, Enzo M Vingolo. The Mozart effect in biofeedback visual rehabilitation: a case report. 46. Steigerwalt RD Jr, Vingolo EM, Plateroti P, et al (2012). The F. Verboschi et al. 290 Functional Neurology 2013; 28(4): 285-291 effect of latanoprost and influence of changes in body position on patients with glaucoma and ocular hypertension. Eur Rev Med PharmacolSci 16:1723-1728. 47. Takanori K, Teruyo T, Masanori H, et al (2009). Fixation behavior in advanced stage glaucoma assessed by the microperimeter MP-1. Jpn J Ophthalmol 53:580-587. 48. Thylefors B, NĂŠgrel AD (1994). The global impact of glaucoma. Bull World Health Organ 72:323-326. 49. Trachtman JN (1978). Biofeedback of accomodation to reduce myopia: a case report. Am J OptomPhysiol Opt 55:400- 406. 50. Trachtman JN (1994). Raccolta dei Risultati Ottenuti in Pazienti a Seguito del Trattamento con l'Allenatore Della Vista Accomotrack Vision Trainer-Riduzione Della Miopia. Atti del XVI corso di aggiornamento Apimo. Montecatini Terme, Italy, 183-195. 51. Varano M, Scassa C (1998). Scanning laser ophthalmoscopemicroperimetry. SeminOphthalmol 13:203-209. 52. Vingolo EM, Cavarretta S, Domanico D, et al (2007). Microperimetric biofeedback in AMD patients. ApplPsychophysiol Biofeedback 32:185-189. 53. Vingolo EM, Salvatore S, Cavarretta S (2009a). Low-vision rehabilitation by means of MP1 biofeedback examination in patients with different macular diseases: a pilot study. ApplPsychophysiol Biofeedback 34:127-133. 54. Vingolo EM, Salvatore S, Grenga PL, et al (2009b). Retinal Degeneration: Causes, Diagnosis and Treatment. New York, Nova Publisher, pp. 249-261. 55. Vingolo EM, Salvatore S, Limoli PG (2013). MP-1 Biofeedback: luminous pattern stimulus versus acoustic biofeedback in age related macular degeneration (AMD). ApplPsychophysiol Biofeedback. 56. Vivian V.Valentin, W.Todd Maddox and F.Gregory Ashby. A computational model of the temporal dynamics of plasticity in procedural learning: sensitivity to feedback timing.