The Effects of Diabetic Retinopathy and Pan-Retinal Photocoagulation on Photoreceptor Cell Function as Assessed by Dark Adaptometry

Purpose The pathophysiology of vision loss in persons with diabetic retinopathy (DR) is complex and incompletely defined. We hypothesized that retinal pigment epithelium (RPE) and rod and cone photoreceptor dysfunction, as measured by dark adaptometry, would increase with severity of DR, and that pan-retinal photocoagulation (PRP) would exacerbate this dysfunction. Methods Dark adaptation (DA) was measured in subjects with diabetes mellitus and healthy controls. Dark adaptation was measured at 5° superior to the fovea following a flash bleach, and the data were analyzed to yield cone and rod sensitivity curves. Retinal layer thicknesses were quantified using spectral-domain optical coherence tomography (OCT). Results The sample consisted of 23 controls and 73 diabetic subjects. Subjects with moderate nonproliferative diabetic retinopathy (NPDR) exhibited significant impairment of rod recovery rate compared with control subjects (P = 0.04). Cone sensitivity was impaired in subjects with proliferative diabetic retinopathy (PDR) (type 1 diabetes mellitus [T1DM]: P = 0.0047; type 2 diabetes mellitus [T2DM]: P < 0.001). Subjects with untreated PDR compared with subjects treated with PRP exhibited similar rod recovery rates and cone sensitivities. Thinner RPE as assessed by OCT was associated with slower rod recovery and lower cone sensitivity, and thinner photoreceptor inner segment/outer segment layer was associated with lower cone sensitivity. Conclusions The results suggest that RPE and photoreceptor cell dysfunction, as assessed by cone sensitivity level and rod- and RPE-mediated dark adaptation, progresses with worsening DR, and rod recovery dysfunction occurs earlier than cone dysfunction. Function was preserved following PRP. The findings suggest multiple defects in retinoid function and provide potential points to improve visual function in persons with PDR.

[1]  P. F. Kauff.  Group , 2000, Elegant Design.

[2]  G. R. Jackson,et al.  Comparison of Visual Function in Older Eyes in the Earliest Stages of Age-related Macular Degeneration to Those in Normal Macular Health , 2016, Current eye research.

[3]  E. Agrón,et al.  Impairments in Dark Adaptation Are Associated with Age-Related Macular Degeneration Severity and Reticular Pseudodrusen. , 2015, Ophthalmology.

[4]  G. R. Jackson,et al.  Multimodal characterization of proliferative diabetic retinopathy reveals alterations in outer retinal function and structure. , 2015, Ophthalmology.

[5]  Sina Farsiu,et al.  Kernel regression based segmentation of optical coherence tomography images with diabetic macular edema. , 2015, Biomedical optics express.

[6]  N. Yoshimura,et al.  Disorganized retinal lamellar structures in nonperfused areas of diabetic retinopathy. , 2015, Investigative ophthalmology & visual science.

[7]  G. Virgili,et al.  Laser photocoagulation for proliferative diabetic retinopathy. , 2014, The Cochrane database of systematic reviews.

[8]  G. R. Jackson,et al.  Twelve-Month Natural History of Dark Adaptation in Patients with AMD , 2014, Optometry and vision science : official publication of the American Academy of Optometry.

[9]  G. R. Jackson,et al.  Associations between abnormal rod-mediated dark adaptation and health and functioning in older adults with normal macular health. , 2014, Investigative ophthalmology & visual science.

[10]  Mei Chen,et al.  Loss of Synaptic Connectivity, Particularly in Second Order Neurons Is a Key Feature of Diabetic Retinal Neuropathy in the Ins2Akita Mouse , 2014, PloS one.

[11]  Á. Szél,et al.  Pathologic alterations of the outer retina in streptozotocin-induced diabetes. , 2014, Investigative ophthalmology & visual science.

[12]  G. R. Jackson,et al.  Effect of doxycycline vs placebo on retinal function and diabetic retinopathy progression in patients with severe nonproliferative or non-high-risk proliferative diabetic retinopathy: a randomized clinical trial. , 2014, JAMA ophthalmology.

[13]  T. Gardner,et al.  Diabetic retinopathy: loss of neuroretinal adaptation to the diabetic metabolic environment , 2014, Annals of the New York Academy of Sciences.

[14]  Ivana K. Kim,et al.  Diagnostic sensitivity and specificity of dark adaptometry for detection of age-related macular degeneration. , 2014, Investigative ophthalmology & visual science.

[15]  K. Palczewski,et al.  Chemistry of the Retinoid (Visual) Cycle , 2013, Chemical reviews.

[16]  Pratul P. Srinivasan,et al.  Fully automatic software for retinal thickness in eyes with diabetic macular edema from images acquired by cirrus and spectralis systems. , 2013, Investigative ophthalmology & visual science.

[17]  B. Klein,et al.  Global Prevalence and Major Risk Factors of Diabetic Retinopathy , 2012, Diabetes Care.

[18]  G. R. Jackson,et al.  Inner retinal visual dysfunction is a sensitive marker of non-proliferative diabetic retinopathy , 2011, British Journal of Ophthalmology.

[19]  S. Kanaly,et al.  Retinal gene expression and visually evoked behavior in diabetic long evans rats. , 2011, Investigative ophthalmology & visual science.

[20]  G. R. Jackson,et al.  Retinal function in relation to improved glycaemic control in type 1 diabetes , 2011, Diabetologia.

[21]  Vladimir J. Kefalov,et al.  The Cone-specific visual cycle , 2011, Progress in Retinal and Eye Research.

[22]  G. R. Jackson,et al.  An integrated approach to diabetic retinopathy research. , 2011, Archives of ophthalmology.

[23]  C. Owsley,et al.  Association between retinal thickness measured by spectral-domain optical coherence tomography (OCT) and rod-mediated dark adaptation in non-exudative age-related maculopathy , 2011, British Journal of Ophthalmology.

[24]  Darren E. Koenig,et al.  The absolute threshold of cone vision. , 2011, Journal of vision.

[25]  G. R. Jackson,et al.  Dark adaptation during transient hyperglycemia in type 2 diabetes. , 2010, Experimental eye research.

[26]  Joseph A. Izatt,et al.  Automatic segmentation of seven retinal layers in SDOCT images congruent with expert manual segmentation , 2010, Optics express.

[27]  S. Kanaly,et al.  Strain-dependent increases in retinal inflammatory proteins and photoreceptor FGF-2 expression in streptozotocin-induced diabetic rats. , 2009, Investigative ophthalmology & visual science.

[28]  G. R. Jackson,et al.  A short-duration dark adaptation protocol for assessment of age-related maculopathy , 2008, Journal of ocular biology, diseases, and informatics.

[29]  A. J. Roman,et al.  Human cone photoreceptor dependence on RPE65 isomerase , 2007, Proceedings of the National Academy of Sciences.

[30]  Eberhart Zrenner,et al.  Hyperoxia, hyperglycemia, and photoreceptor sensitivity in normal and diabetic subjects , 2006, Visual Neuroscience.

[31]  N. Drasdo,et al.  Silent substitution S‐cone electroretinogram in subjects with diabetes mellitus , 2005, Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians.

[32]  T. Lamb,et al.  Dark adaptation and the retinoid cycle of vision , 2004, Progress in Retinal and Eye Research.

[33]  Matthew D. Davis,et al.  Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. , 2003, Ophthalmology.

[34]  V. Parisi,et al.  Visual electrophysiological responses in persons with type 1 diabetes , 2001, Diabetes/metabolism research and reviews.

[35]  Cynthia Owsley,et al.  Using nonlinear regression to estimate parameters of dark adaptation , 1999, Behavior research methods, instruments, & computers : a journal of the Psychonomic Society, Inc.

[36]  T. Lamb,et al.  Molecular basis of dark adaptation in rod photoreceptors , 1998, Eye.

[37]  R. Carr,et al.  Evidence for photoreceptor changes in patients with diabetic retinopathy. , 1997, Investigative Ophthalmology and Visual Science.

[38]  R. Carr,et al.  Effects of Early Diabetic Retinopathy on Rod System Sensitivity , 1993, Optometry and vision science : official publication of the American Academy of Optometry.

[39]  J. Weiter,et al.  The macular photostress test in diabetic retinopathy and age-related macular degeneration. , 1990, Archives of ophthalmology.

[40]  A. Hendrickson,et al.  Human photoreceptor topography , 1990, The Journal of comparative neurology.

[41]  E. Midena,et al.  Macular recovery function (nyctometry) in diabetics without and with early retinopathy. , 1990, The British journal of ophthalmology.

[42]  M. Mäntyjärvi.  Colour vision and dark adaptation in diabetic patients after photocoagulation , 1989, Acta ophthalmologica.

[43]  G. Fishman,et al.  Prolonged rod dark adaptation in retinitis pigmentosa. , 1984, The British journal of ophthalmology.

[44]  H. Larsen,et al.  NYCTOMETRY ‐ A NEW SCREENING METHOD FOR SELECTION OF PATIENTS WITH SIMPLE DIABETIC RETINOPATHY WHO ARE AT RISK OF DEVELOPING PROLIFERATIVE RETINOPATHY: Results of a 3‐year Follow‐up , 1983, Acta ophthalmologica.

[45]  D. Henson,et al.  Dark adaptation in diabetes mellitus. , 1979, The British journal of ophthalmology.

[46]  M. Lavail,et al.  Rhodopsin content and rod outer segment length in albino rat eyes: modification by dark adaptation. , 1978, Experimental eye research.

[47]  T. Amemiya.  Dark adaptation in diabetics. , 1977, Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde.

[48]  B. Zetterström,et al.  PHOTOCOAGULATION IN DIABETIC RETINOPATHY WITH SPECIAL REFERENCE TO ITS EFFECT ON DARK ADAPTATION , 1973, Acta ophthalmologica.