Recent Advances in Ophthalmology (Volume 11) HV Nema, Nitin Nema
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1Recent Advances in Ophthalmology—11
2Recent Advances in Ophthalmology—11
Editors HV Nema MS Former Professor and Head Department of Ophthalmology Banaras Hindu University Varanasi, Uttar Pradesh, India Nitin Nema MS DNB Associate Professor Department of Ophthalmology Sri Aurobindo Institute of Medical Sciences Indore, Madhya Pradesh, India Editorial Board Jorge L Alió MD PhD Alicante, Spain Suresh Chandra MD Madison, USA J Biswas MS FAMS Chennai, Tamil Nadu, India Frank Goes MD Antwerp, Belgium Lingam Gopal MS FRAS Chennai, Tamil Nadu, India Devindra Sood MD New Delhi, India
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Recent Advances in Ophthalmology—11
First Edition: 2013
9789350904350
Printed at
4Dedicated to
The Loving Memory of Pratibha
5Contributors
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7
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Preface
Advances in the field of ophthalmology are rapid and ever-increasing. It is impossible to cover all advances occurring every year in a small volume. Therefore, like previous series, Recent Advances of Ophthalmology—11 contains some selected chapters on glaucoma, lens, retina, and systemic diseases. Approximately 50% of chapters deal with diseases of the retina, some are common and some rare. Two out of three editorials are on retina. Retinopathy of prematurity, macular hole, macular dystrophy, central serous chorioretinopathy, proliferative vitreoretinopathy, and retinal vascular occlusion are challenging problems. They may cause loss of vision if not managed properly.
Earlier macular hole was considered untreatable, but now with better surgical techniques, it can be managed with encouraging results. The subject is comprehensively reviewed by Meena and coworkers. Kulkarni and Chandra suggested certain tips to further improve the results of the macular hole surgery.
Readers may find the editorial on artificial retinal implants interesting. The ongoing pilot researches indicate that implantation of biomedical devices can restore some useful vision in patients with RP or AMO. Can the blind see again with the implant? Studies conducted on a large number of cases with long follow-up can provide a valid answer.
Every year, hundreds of research articles are published on the diagnosis and treatment of glaucoma. But how to assess and arrest the progress of glaucoma is not adequately explored, although it is an essential component of glaucoma management. Murali Ariga discussed the problem briefly in Chapter 3 on Progression of Optic Disk and Visual Field Changes in Glaucoma. Halting the progression of glaucomatous damage is likely to retain good visual acuity and visual fields in patients with glaucoma. The progression of glaucoma can be determined by periodic visual field recordings. Both event-based (glaucoma progress analysis) and trend-based analyses (rate of progression) should be determined with the help of Humphrey VF Analyzer. The progression analysis of the retinal nerve fiber layer parameters obtained from time domain OCT should also be taken into consideration. Harsha and Chandra Sekhar emphasized the importance of 9objective diagnosis of glaucoma with the help of modern technology not in isolation but in combination with complete clinical picture.
Two chapters on collagen disorders—Ocular Involvement in Systemic Rheumatic Diseases and Giant Cell Arteritis—and one on HIV and Opportunistic Infections of eye have been included in this volume. They provide enough insight about close interrelationship between the eye and systemic diseases.
Indeed recent developments in ophthalmology have revolutionized the treatment of eye diseases and considerably improved the quality of life of the patients. Hopefully, the postgraduate students in ophthalmology and general ophthalmic practitioners will find the present series helpful not only in the basic understanding of new developments in the subject but also in day-to-day clinical practice and care of the patients.
HV Nema
Nitin Nema
10Acknowledgments
We are indebted to the contributors of Recent Advances of Ophthalmology—11 for their timely and scholarly contributions.
We would like to record our sincere thanks to Dr Amol Kulkarni, Professor Suresh Chandra, Dr Harsha H Rao, Dr G Chandra Sekhar and Dr Rajat Agarwal for contributing enlightening editorials.
Shri Jitendar P Vij (Group Chairman), Mr Ankit Vij (Managing Director) of M/s Jaypee Brothers Medical Publishers (P) Ltd, New Delhi, India and especially Mr Tarun Duneja (Director- Publishing) deserve our sincere thanks for their continued interest in the publication of the Recent Advances in Ophthalmology series.
13Editorial
Role of Technology in the Diagnosis of Glaucoma and Assessing its Progression
Harsha L Rao, Chandra Sekhar Garudadri
Glaucoma is the second leading cause of blindness worldwide. As clinicians, we not only owe the best possible care to the patients who seek medical help but also a responsibility towards those undetected and improperly treated. The current status of glaucoma care in the world is aptly summarized as follows: more than 50% of glaucoma in the community is undiagnosed (in the developing countries, this would be higher than 90%), more than 50% of those undiagnosed would have seen an eyecare provider in the recent past, more than 50% taking medications do not need them (over treated), and finally 50% of those advised medication do not use them. Missed diagnoses in those previously examined by an eyecare professional, (in the “system”) is attributable to lack of comprehensive evaluation and appropriate clinical skills. The recent advances in the imaging of the optic nerve head seek to achieve an early and “objective” diagnosis of glaucoma. One of the reasons for overdiagnosis is using the results of these technologies exclusively and not in the context of complete clinical picture.
 
DIAGNOSIS
Imaging of the optic nerve head and retinal nerve fiber layer are widely reported to be useful in glaucoma diagnosis. One could (naively) argue that the imaging tests are objective and can be performed easily in uncooperative patients (since they are quick and need little attention) as opposed to standard automated perimetry (SAP) that is the current standard but time consuming and difficult due to the subjective nature of the test. Further, as it is reported that 20–40% retinal ganglion cells could be lost before a visual field defect could be picked up by SAP, these new imaging technologies can theoretically aid in the early diagnosis of glaucoma. This rationale needs not necessarily convert to a clinical reality. The reported sensitivity and specificity of these technologies and their agreement with each other are far from ideal. The sensitivity (ability to diagnose the disease correctly — PID: positive in disease) of the best parameter for each of the imaging technologies at a fixed specificity (NIH: negative in health 14or ability to declare a normal subject as not having the disease) of 95% (labeling only 5 as abnormal out of hundred normal subjects) varies from 36 to 72%. This means that the imaging technologies fail to diagnose glaucoma in as many as 28–64% of the eyes with established abnormality on SAP. While we perform these investigations with the idea of either establishing or ruling out a disease, we fail to realize that there is a cost-benefit ratio even in diagnostic testing. These tests are expensive, there are risks of overdiagnosis with the attendant effect of labeling, and there are problems with interpretation (the normative database of the machine used for diagnostic classification is often limited to small number of subjects and few ethnicities and hence may not be appropriate to apply for testing patients of all ethnicities). We have reported that the incorporation of the Indian normative database does not improve the diagnostic ability of HRT3.
In addition to the above limitations, bias in the ability of imaging devices to diagnose glaucoma can arises from multiple other sources. Optic disk size has been shown to be a confounder in the diagnostic accuracy of HRT., Delineation of the optic disk margin and measurement circle placement have been shown to be confounders in the diagnostic ability of these instruments. Reporting the diagnostic ability in glaucoma patients while using a set of totally normal subjects as controls, also is shown to artifactually inflate the sensitivity of these instruments. This is because a diagnostic test in clinical practice is used in situations, which arouse a suspicion of the disease and not in situations where the diagnosis of a disease is easy to either rule in or rule out by clinical examination.
Garway-Heath and Friedman appropriately stated, “Devices cannot diagnose our patients’ conditions, but the findings they provide frequently alter the probability that a subject has a particular condition”. Thus devices cannot be a substitute for poor clinical skills but at best a complement to good clinical evaluation. If after a good and comprehensive clinical evaluation, the probability (pre-test probability) of the disease is around 20%, it is futile to perform any diagnostic test, as even a positive result cannot confirm the presence of the disease. On the other hand, if the probability of the disease is about 80% after a good clinical examination (the need for testing is not to diagnose but probably to establish a baseline for follow-up), even a negative test result cannot rule out the disease. It is in the intermediate range, when the probability of disease is around 50% that the diagnostic test result would strongly help in the diagnostic decision. Before ordering a diagnostic test, it is useful to ask ourselves as to how our course of action would change on the basis of the test result. The probability of the disease before and after the diagnostic test 15can be mathematically calculated using the likelihood ratio (LR) of the test result in consideration. If we want to use the results of the diagnostic tests appropriately, estimating the LR is the best way around. Thus, it is important for us to know the LRs associated with different test results before investing in a new diagnostic test.
The principle behind the use of the likelihood ratios is the calculation of the increase in the probability of a given diagnosis given the prior probability of the disease (based on complete clinical evaluation or the prevalence of the disease) and the result of the diagnostic test with its likelihood ratio. This principle is applicable not only for the diagnosis of a disease but also for any event. This principle in mathematical terms is called the Bayesian theorem. Keeping the mathematics aside, the concept is very intuitive and we keep using this in our daily lives extensively, albeit without the mathematical calculations or the complex terminologies.
For example, on a cloudy day during the rainy season, if it rains we say “it is bound to happen” and if it did not rain, one might say “that was very unlikely” or some such thing. If a 25-year-old healthy, prospective, army recruit ends up with an ST segment change on ECG, one would suspect the test or the machine, as the likelihood of this young, healthy man having ischemic heart disease (IHD) is very low. The same result in a 60-year-old gentleman with diabetes and hypertension with precordial discomfort on exertion would be diagnostic of IHD. The prior probability of IHD is very high in the latter and very low in the former. This explains why the same test result is interpreted differently in different situations.
 
PROGRESSION
Halting progression of glaucomatous damage during the lifetime of the patient, with minimum effect on the quality of life, is one of the main objectives of any glaucoma treatment. But judging glaucoma progression is a challenging task. Progression of glaucoma is known to occur at variable pace. The untreated arm of the Early Manifest Glaucoma Treatment (EMGT) trial is a great source information of the natural history of glaucoma. It was found in the EMGT trial that untreated normal tension glaucoma in the younger age group had the least rate of progression (never progressing to blindness from normal vision) and pseudoexfoliation glaucoma in the elderly group could progress to blindness from normal vision in a little less than 2 years.
The standard method to detect glaucoma progression is to monitor the visual field (VF) defects periodically for change. Two commonly used approaches to detect change in VF defects over time are the event-based 16and the trend-based progression analyses. Event-based analysis determines VF progression to be either present or absent depending on a predefined change in the VF parameters. Trend-based analysis provides the actual rate of change of VF parameters. In clinical practice, information from both these analyses is important, because it is not only sufficient to identify VF progression in glaucoma but also to determine the rate of progression, so that the treatment can be more aggressive in patients that progress rapidly. The recently introduced Guided Progression Analysis by the Humphrey VF Analyzer (Carl Zeiss Meditec, Inc. Dublin, CA) provides both an event-based progression analysis and a trend-based analysis on the same printout. The event-based progression analysis, called the glaucoma progression analysis (GPA), is based on the criteria designed to identify VF progression in the EMGT. Trend-based progression analysis is based on the rate of progression (ROP) of the visual function of the eye through a linear regression model using a new global index, visual field index (VFI). The VFI is the aggregate percentage of visual function for a given field at each point where the visual thresholds are estimated. VFI is calculated from pattern deviations in eyes with a mean deviation (MD) of better than −20 dB and from total deviations in eyes with a MD worse than −20 dB. The central points in visual field have more weight than peripheral points. VFI is also shown to be less affected by media opacities like cataract.
Though most of the imaging technologies have both event- and trend- based algorithms to judge structural progression in glaucoma, their usefulness needs to be validated, and there is no consensus on what constitutes a significant structural change clinically. HRT topographic change analysis (TCA) is the most well developed and tested progression detection analysis available for optical imaging techniques. Glaucoma progression algorithms on GDx are called GDx GPA. Time domain OCT also has progression analysis of the RNFL parameters. The agreement between the structural changes of these imaging technologies and the visual field parameters have been reported to be moderate to poor. 16–22 Longitudinal data of the anatomical changes on the imaging technologies subsequently converting to filed changes is available only for HRT from the OHTS. We believe that the gold standard for assessing glaucoma progression continues to be the standard automated perimetry.
In conclusion, in establishing the diagnosis and progression of glaucoma, advances in the imaging technologies of the optic nerve are a complement to a good and comprehensive clinical evaluation and cannot be a substitute. The results of these tests need to be interpreted in the context of the remaining clinical picture and not in isolation.17
REFERENCES
  1. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90:262–7.
  1. Vijaya L, George R, Arvind H, et al. Prevalence of angle-closure disease in a rural southern Indian population. Arch Ophthalmol. 2006;124:403–9.
  1. Vaahtoranta-Lehtonen H, Tuulonen A, Aronen P, et al. Cost effectiveness and cost utility of an organized screening programme for glaucoma. Acta Ophthalmol Scand. 2007;85:508–18.
  1. Thomas R, Dogra M. An evaluation of medical college departments of ophthalmology in India and change following provision of modern instrumentation and training. Indian J Ophthalmol. 2008;56:9–16.
  1. Garway-Heath DF, Friedman DS. How should results from clinical tests be integrated into the diagnostic process? Ophthalmology. 2006;113:1479–80.
  1. Kanamori A, Nagai-Kusuhara A, Escano MF, Maeda H, Nakamura M, Negi A. Comparison of confocal scanning laser ophthalmoscopy, scanning laser polarimetry and optical coherence tomography to discriminate ocular hypertension and glaucoma at an early stage. Graefes Arch Clin Exp Ophthalmol. 2006;244:58–68.
  1. Rao HL, Babu GJ, Sekhar GC. Comparison of the diagnostic capability of the Heidelberg Retina Tomographs 2 and 3 for glaucoma in the Indian population. Ophthalmology. 2010;117:275–81.
  1. Medeiros FA, Zangwill LM, Bowd C, Sample PA, Weinreb RN. Influence of disease severity and optic disc size on the diagnostic performance of imaging instruments in glaucoma. Invest Ophthalmol Vis Sci. 2006;47:1008–15.
  1. Garudadri CS, Rao HL, Parikh RS, et al. Effect of Optic Disc Size and Disease Severity on the Diagnostic Capability of Glaucoma Imaging Technologies in an Indian Population. J Glaucoma.  2011.
  1. Gabriele ML, Ishikawa H, Wollstein G, et al. Optical coherence tomography scan circle location and mean retinal nerve fiber layer measurement variability. Invest Ophthalmol Vis Sci. 2008;49:2315–21.
  1. Medeiros FA, Ng D, Zangwill LM, Sample PA, Bowd C, Weinreb RN. The effects of study design and spectrum bias on the evaluation of diagnostic accuracy of confocal scanning laser ophthalmoscopy in glaucoma. Invest Ophthalmol Vis Sci. 2007;48:214–22.
  1. Heijl A, Bengtsson B, Hyman L, Leske MC. Natural history of open-angle glaucoma. Ophthalmology. 2009;116:2271–6.
  1. Leske MC, Heijl A, Hyman L, Bengtsson B. Early Manifest Glaucoma Trial: design and baseline data. Ophthalmology. 1999;106:2144–53.
  1. Bengtsson B, Heijl A. A visual field index for calculation of glaucoma rate of progression. Am J Ophthalmol. 2008;145:343–53.
  1. Rao HL, Jonnadula GB, Addepalli UK, Senthil S, Garudadri CS. Effect of Cataract Extraction on Visual Field Index in Glaucoma. J Glaucoma.  2011.
  1. Chauhan BC, Nicolela MT, Artes PH. Incidence and Rate of Glaucomatous Visual Field Progression After Optic Disc Change Measured With Scanning Laser Tomography [ARVO abstract]. Invest Ophthalmol Vis Sci.  2009;50:E-Abstract 2574.
  1. Chauhan BC, McCormick TA, Nicolela MT, LeBlanc RP. Optic disc and visual field changes in a prospective longitudinal study of patients with 18glaucoma: comparison of scanning laser tomography with conventional perimetry and optic disc photography. Arch Ophthalmol. 2001;119:1492–9.
  1. Bowd C, Balasubramanian M, Weinreb RN, et al. Performance of confocal scanning laser tomograph Topographic Change Analysis (TCA) for assessing glaucomatous progression. Invest Ophthalmol Vis Sci. 2009;50:691–701.
  1. O'Leary N, Crabb DP, Mansberger SL, et al. Glaucomatous progression in series of stereoscopic photographs and Heidelberg retina tomograph images. Arch Ophthalmol. 2010;128:560–8.
  1. Alencar LM, Zangwill LM, Weinreb RN, et al. Agreement for detecting glaucoma progression with the GDx guided progression analysis, automated perimetry, and optic disc photography. Ophthalmology. 2010;117:462–70.
  1. Grewal DS, Sehi M, Greenfield DS. Comparing rates of retinal nerve fibre layer loss with GDxECC using different methods of visual-field progression. Br J Ophthalmol. 2011;95:1122–7.
  1. Leung CK, Cheung CY, Weinreb RN, et al. Evaluation of retinal nerve fiber layer progression in glaucoma: a study on optical coherence tomography guided progression analysis. Invest Ophthalmol Vis Sci. 2010;51:217–22.
  1. Weinreb RN, Zangwill LM, Jain S, et al. Predicting the onset of glaucoma: the confocal scanning laser ophthalmoscopy ancillary study to the Ocular Hypertension Treatment Study. Ophthalmology. 2010;117:1674–83.
19Editorial
Macular Hole
Amol D Kulkarni, Suresh R Chandra
Neil Kelly and Rob Wendell reported a relatively high success rate in the cure of macular holes previously considered beyond repair. Since that time, surgical techniques have improved and success rates have increased. The pathogenesis of macular holes is not well understood. Various theories exist regarding the etiology of macular holes including trauma, cystic degeneration and vitreous traction. It is likely that macular holes represent a heterogeneous group of conditions with a common final pathway and similar clinical manifestation. The vitreous exerts anteroposterior traction, tangential traction, or both which is thought to be critical in the pathogenesis of a macular hole. Gass classified macular hole into various stages precisely defined by OCT which is now the diagnostic modality of choice for this condition. Furthermore, OCT is a useful aid in patient education to demonstrate the presence of the macular hole and the postoperative result. The current anatomic success rates range from 82 to 100%. There is relief of traction (tangential and A-P) and stimulation of fibroglial proliferation to plug the hole after vitrectomy and gas tamponade.
Dr Meena has written an excellent comprehensive review of pathophysiology, diagnosis, and management of macular holes. There is detailed description of OCT staging of macular hole. She specifically highlights the various controversies that exist regarding the surgical management of macular holes.
Our recommendations include:
  1. Timing of surgical intervention: Surgical results are best for macular holes of less than 1 year duration. Given that chronic holes may do well, it is reasonable to offer surgery for macular holes of 1–5 years duration.
  2. Stage of the macular hole: It is best to observe stage 1 and lamellar macular hole and monitor for progression. Surgical management is recommended with documentation of a stage 2 or higher, full-thickness macular hole.20
  3. Internal limiting membrane peeling: The removal of internal limiting membrane (ILM) is considered to be a contributing factor in the success of macular hole surgeries. ILM peeling also removes any contractile epiretinal membrane (ERM), thereby, relieving tangential traction. In addition, membrane removal can enhance mobility of the hole edges, thereby, facilitating reapproximation. Several retrospective studies suggest that ILM peeling is beneficial in attaining improved visual acuity and anatomic closure in macular holes of less than six months duration. However, there has been some concern regarding damage to the retina secondary to membrane peeling. The absence of a large randomized clinical trial likely accounts for the lack of consensus regarding the efficacy of and indications for ILM peeling.
  4. Use of vital dyes for internal limiting membrane peeling: Indocyanine green (ICG) dye was the first vital dye used for macular surgery. There is considerable literature questioning the toxicity of ICG dye to the retina and retinal pigment epithelium (RPE). Despite the laboratory and literature cautioning the use of ICG dye, an equal amount of literature documented good surgical and visual results. ICG dye is still used by surgeons with care taken to limit the exposure of the retina and, potentially more importantly, the RPE to the dye. Trypan blue has been used to stain the ILM; however, it does not appear to stain as effectively as ICG dye. Triamcinolone acetonide has also been used to facilitate peeling of the ILM. Brilliant blue G is a newly introduced vital dye which is less toxic to the retinal pigment epithelium and stains both ERM and ILM as well. It has been comparable to ICG in terms of ILM staining and ease of surgical removal.
  5. Adjuvants for macular hole surgery: An assortment of adjuvant therapies has been used at the time of surgery in an effort to enhance glial proliferation. These include transforming growth factor beta (TGF-ß), autologous platelets, autologous plasmin, and plasmin. Prospective randomized studies of TGF-ß and autologous platelets have, however, shown little benefit in terms of anatomic closure or final visual acuity. Hence, their use has not gained much popularity.
  6. Intraocular tamponade: The primary difference achieved using different gases is the duration of action of the gas bubble and, consequently, the amount of internal tamponade achieved within the first several days after surgery. Longer acting gas like C3F8 allows for 2–3 weeks of contact between hole and gas if supine position is avoided. Hence, there is more leeway in positioning. Shorter acting gas therefore requires more rigorous positioning to achieve hole/gas contact as bubble dissipates. 21Positioning may actually be more critical as the bubble dissipates. Majority of surgeons uses C3F8 (64% C3F8 versus 33% SF6). Intraocular tamponade with C3F8 gas produces 6 weeks of visual debility, which is as cumbersome to the patient as the prone positioning.
  7. Duration for face-down prone positioning: Historically, strict face-down positioning had been recommended for patients for up to 4 weeks, with consequent difficulties of compliance and patient's quality of life during that period. Majority of surgeons advocates at least 2 weeks of face-down positioning. The advent of ILM peeling has reduced the number of days for face-down positioning. Extended periods of face down positioning often produce neck or back pain. There have been reports of complications, including ulnar nerve neuropathy and pressure sores. In addition to these medical complications, there are the financial costs of lost time from work, caregiver requirements, and expensive medical equipment. A shortened prone positioning period offers patients decreased risk of medical complication, increases patient convenience, and lowers the indirect costs of macular hole surgery.
  8. 20-gauge versus small gauge vitrectomy systems: While no one system poses a significant long-term advantage, smaller gauge vitrectomy systems, with frequently self-sealing wounds, avoid induced astigmatism from suturing sclerotomies, resulting in a more rapid recovery of vision. An initial increase in endophthalmitis appears to have been addressed by changing the means of wound construction but may still be considered a disadvantage to small gauge vitrectomy systems.
In conclusion, the advent of vitreoretinal-microsurgical techniques has sparked a renewed interest in idiopathic macular hole and, particularly, its management. There is still a need to develop new techniques to improve visual outcomes, enhance patient convenience, and diminish complications. New diagnostic modalities, such as ultra-high resolution OCT and adaptive optics will improve our understanding of the cellular repair process following macular hole surgery. This may help us understand pathogenesis of macular hole at molecular level and consider the role of neuroprotection and photoceptor rescue to further improve the visual function.
REFERENCES
  1. Wolf S, Wolf-Schnurrbusch U. Spectral-domain optical coherence tomography use in macular diseases: a review. Ophthalmologica. 2010;224(6):333–40.
  1. Bainbridge J, Herbert E, Gregor Z. Macular holes: vitreoretinal relationships and surgical approaches. Eye. 2008;22(10):1301–9.
  1. Lois N, Burr J, Norrie J, at al. Internal limiting membrane peeling versus no peeling for idiopathic full-thickness macular hole: a pragmatic randomized controlled trial. Invest Ophthalmol Vis Sci. 2011;52(3):1586–92.
  1. 22 Shukla D, Kalliath J, Neelakantan N, et al. A comparison of brilliant blue G, trypan blue, and indocyanine green dyes to assist internal limiting membrane peeling during macular hole surgery. Retina. 2011;31(10):2021–5.
  1. Nam Y, Chung H, Lee JY, et al. Comparison of 25- and 23-gauge sutureless microincision vitrectomy surgery in the treatment of various vitreoretinal diseases. Eye. 2010;24(5):869–74.
23Editorial
Artificial Retinal Implants: Can the Blind Really See Again?
Rajat N Agrawal
Improvement and restoration of a lost bodily function has always been a goal for physicians and researchers. From the philosophical works of Robert Hooke predicting use of mechanical devices, which would improve special senses to an English surgeon, CH Wilkinson, in 1799 advertising “medico-electric” rooms, where patients could be treated for a variety of ailments, including blindness, there have been various attempts at trying to offer some form of treatment and rehabilitation for people who become blind due to various etiologies. These attempts, though conjectural, demonstrated the understanding from scientists— perspective that electricity may have therapeutic uses in a human body and have now resulted in using biomedical devices, such as cardiac pacemakers and cochlear implants routinely in medicine. Success of these implantable devices and improved technology provided the feasibility for the idea of the development of a visual prosthesis that could help blind people.
Löwenstein and Borchardt, in 1918, initially demonstrated that the position of electrically induced visual percepts within the visual field was systematically related to the area of the occipital lobe that received the electrical stimulation. This visual percept was described as a phosphene. This formed the basis of the field of cortical implants, leading to implantation of 80-electrode device by Giles Brindley and colleagues in London in 1968 in a 52-year-old woman blind from glaucoma. This was the first serious effort in the field of artificial vision.
Experiments in the early 1970s demonstrated that ocular stimulation, via a contact lens stimulating electrode, could allow blind humans to perceive electrically elicited phosphenes. These responses indicated the presence of at least some functioning inner retinal cells in the subjects. A number of retinal disorders that lead to blindness, such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD) have been morphometrically studied and have been found to have significant numbers of inner retinal cells still present even in advanced stages of the disease.– On average, 78% of the inner nuclear layer cells and 30% of the ganglion cells were 24found to remain histologically intact in a patient with advanced RP, although this will obviously vary from subject to subject. Similar results were found in AMD patients. Thus, the remaining cells act as a “platform” for implantation of the artificial retinal prosthesis that is based on the premise that electrically stimulating the still functional inner retinal neurons in RP and AMD will help restore at least some level of vision.
There are currently many groups around the world involved in the development of retinal prostheses. The position of the electrode device and the stimulating array in relation to the retina defines the nomenclature of the groups. The two leading groups in epiretinal prosthesis (implant fixed in front of the retina) are the group from Doheny Eye Institute at the University of Southern California working with Second Sight Medical Products Inc. (USC-SSMP) in the United States and the other group is led by Intelligent Medical Implant GmbH (IMI) in Switzerland. Both are currently in clinical trials. The subretinal prosthesis (implant placed in the subretinal space between the neurosensory retina and the retinal pigment epithelium) work is led by the German Consortium coordinated by Zrenner in Tubingen, while Rizzo from Massachusetts Eye and Ear Infirmary along with Wyatt heads the other group. Another group in Japan has made significant progress on a suprachoroidal transretinal approach, which places the device in the suprachoroidal space for stimulation, while an Australian consortium is experimenting with the development of the device, and is likely to implant in their first patient in 2013.
Currently, the epiretinal work of USC-SSMP is at the most advanced stage, while most of the other groups are still in clinical trials. The device, ARGUS-II,™ has received CE mark in Europe, which signifies that it can be sold commercially in Europe. The device (and most other devices in development) is indicated only for very advanced stages of retinitis pigmentosa. Macular degeneration (AMD) is considered to be the other disease of interest, but due to the delayed or rare nature of complete loss of vision in those eyes, this device is not permitted for implantation in AMD patients.
In general, the devices of most groups around the world work on the following principle: a video camera placed on a pair of glasses convert visual image into electrical impulses, which undergo processing before being sent to a surgically implanted device in the eye close to the retina. The electrodes release an electrical charge (which has been found to be safe to the retina), which creates an electrical potential that gets carried through a functioning optic nerve to the occipital cortex, thus, allowing a blind patient to see phosphenes. The pattern of phosphenes allows a patient to make sense of what he/she is seeing in front of him, which needs 25a little amount of training, considering the fact that these patients have not had functional sight for more than 15–20 years at least.
The ARGUS-II™ technology consists of 60 electrodes, with the device being placed epiretinally via a surgical procedure that is akin to a vitrectomy-scleral buckle approach in retinal surgical. A conductive coil is placed on the sclera, that also contains telemetry equipment, which allows information to be sent and received, and power to be received from another coil placed on special glasses.
More than 30 patients with advanced RP have been implanted with this device with the surgical outcomes being achieved in majority of patients. Most of these patients are able to navigate independently, without assistance or with a cane, and are also able to perform activities of daily living, such as sorting washed laundry. The actual improvement in terms of vision and field of vision is difficult to grasp, since they are not quantifiable by the routine methods of investigation we use in the clinic. In spite of that, we have noted a marked improvement in functionality of these implanted patients.
There has been an ongoing serious attempt to get the device to India soon, while also working on a proposal to develop an Indian bionic eye, built in India, specifically with the need and requirement of Indian patients in mind.
Dating from the time almost 50 years ago when it was first found that electrical stimulation of the retina would generate phosphenes in patients— eyes, the work has been able to demonstrate significant progress with the 60-electrode device. The USC-SSMP team is working on a 1000-electrode device that is likely to give significant visual information to a blind subject. In particular, it is hoped that face recognition and reading ability will be restored allowing for mainstreaming of many blind patients and vastly improvement in the quality of life.
REFERENCES
  1. Weiland JD, Humayun MS. Past, present, and future of artificial vision. Artif Organs. 2003;27:961–2.
  1. Stone JL, Barlow WE, Humayun MS, de Juan E, Jr., Milam AH. Morphometric analysis of macular photoreceptors and ganglion cells in retinas with retinitis pigmentosa. Arch Ophthalmol. 1992;110:1634–9.
  1. Santos A, Humayun MS, de Juan E, Jr., Greenburg RJ, Marsh MJ, Klock IB, Milam AH. Preservation of the inner retina in retinitis pigmentosa. A morphometric analysis. Arch Ophthalmol. 1997;115:511–5.
  1. Kim SY, Sadda S, Humayun MS, de Juan E, Jr., Melia BM, Green WR. Morphometric analysis of the macula in eyes with geographic atrophy due to age-related macular degeneration. Retina. 2002;22:464–70.
  1. 26 Kim SY, Sadda S, Pearlman J, Humayun MS, de Juan E, Jr., Melia BM, Green WR. Morphometric analysis of the macula in eyes with disciform age-related macular degeneration. Retina. 2002;22:471–7.
  1. Weiland JD, Cho AK, Humayun MS. Retinal prostheses: current clinical results and future needs. Ophthalmology. 2011;118:2227–37.
  1. Eng JG, Agrawal RN, Tozer KR, Ross-Cisneros FN, Dagnelie G, Greenberg RJ, et al. Morphometric analysis of optic nerves and retina from an end-stage retinitis pigmentosa patient with an implanted active epiretinal array. Invest Ophthalmol Vis Sci. 2011;52:4610–6.
  1. Chader GJ, Weiland J, Humayun MS. Artificial vision: needs, functioning, and testing of a retinal electronic prosthesis. Prog Brain Res. 2009;175:317–32.