Ocular manifestation in DM - H.pptx

education

1. Ocular Manifestations of Diabetes Mellitus Presenter Harshita Thapa Bachelor in Optometry (Second Year) Moderator Niraj Dev Joshi Suraj Chhetri

2. Objectives To discuss about the different types of ocular manifestations of diabetes mellitus (hyperglycemia) To understand the pathogenesis of various ocular complications caused by diabetes mellitus

3. Presentation Layout Introduction Classification Different ocular structures affected by Diabetes Mellitus Visual implications of Diabetic Retinopathy & Diabetic Maculopathy Summary References

4. What is Diabetes? Defined as heterogeneous metabolic disorder characterized by : Chronic hyperglycemia with disturbance of carbohydrate, fat and protein metabolism Resulting from defects in insulin secretion, impaired effectiveness of insulin action, or both

5. Classification Type I diabetes (Insulin Dependent Diabetes Mellitus) Type II diabetes (Non-Insulin Dependent Diabetes Mellitus) Gestational diabetes mellitus  Drug or chemical induced hypoglycaemia Disease of exocrine pancreas; pancreatitis or carcinoma Maturity onset diabetes in young Source: Eye essentials (Chris Steele)

6. Mainly classified as :    Type I Diabetes Mellitus   Aka insulin dependent diabetes or juvenile onset diabetes  Basic phenomenon is destruction of beta cell mass leading to absolute insulin deficiency       Type II Diabetes Mellitus   Aka non-insulin dependent  diabetes or maturity onset diabetes   Basic metabolic defect is either a delayed insulin secretion relative to glucose load (impaired insulin secretion) or peripheral tissues are unable to respond to insulin (insulin resistance)  

7. What are the ocular structures affected by diabetes mellitus? RETINA Diabetic retinopathy Diabetic maculopathy

8. Tear film abnormalities The incidence of dry eye is correlated with the level of glycated hemoglobin : the higher the level of glycated hemoglobin , the higher the incidence of dry eye .1 Causes epithelial barrier dysfunction subsequently leading to corneal complications and then LFU dysfunction. 2 1 Zhao Z, Liu J, Shi B, He S, Yao X, Willcox MD. Advanced glycation end product (AGE) modified proteins in tears of diabetic patients. Molecular Vision. 2010;16:1576. 2 Gekka M, Miyata K, Nagai Y, Nemoto S, Sameshima T, Tanabe T, Maruoka S, Nakahara M, Kato S, Amano S. Corneal epithelial barrier function in diabetic patients. Cornea. 2004 Jan 1;23(1):35-7.

9. Tear film abnormalities Accumulation of sorbitol within cells; cellular  edema  and dysfunction, results in lacrimal gland structure damage/dysfunction and the induction of decreased tear secretion. 3 Reduction of the number of goblet cells; reduces mucin production and the hydrophilic nature of the ocular surface leading to tear film instability 3 3 Tseng SC, Hirst LW, Maumenee AE, Kenyon KR, Sun TT, Green WR. Possible mechanisms for the loss of goblet cells in mucin-deficient disorders. Ophthalmology. 1984 Jun 1;91(6):545-52.

10. Abnormalities of Lids and Conjunctiva Xanthelasma : Lipid deposition in dermis of lid Recurrent styes and blepharoconjunctivitis Telangiectasia ,sludging of the blood in conjunctival vessels Subconjunctival haemorrhage

11. Corneal abnormalities Corneal sensitivity commonly impaired ; neuropathy of ophthalmic division of trigeminal nerve causes neurotrophic keratopathy resulting in loss of sensory innervation to cornea 1 Intrinsic abnormalities of epithelial basement membrane complexes with, impaired barrier function leads to Superficial punctate keratitis Poor healing after trauma and Formation of persistent epithelial defect 2 1 Gyawali R, Toomey M, Stapleton F, Zangerl B, Dillon L, Keay L, Liew G, Jalbert I. Quality of the Australian National Health and Medical Research Council’s clinical practice guidelines for the management of diabetic retinopathy. Clinical and Experimental Optometry. 2021 Nov 17;104(8):864-70 2 Hyndiuk RA, Kazarian EL, Schultz RO, Seideman S. Neurotrophic corneal ulcers in diabetes mellitus. Archives of Ophthalmology. 1977 Dec 1;95(12):2193-6.

12. Pupil abnormalities Rigid Pupil- Difficulty in mydriasis Due to autonomic neuropathy Partially denervating both the sphincter and the dilator muscles

13. Refractive instability in diabetes Transient changes or fluctuations in vision and prescription can be a key sign of impaired glucose control 1 In case of increased blood glucose level ,myopic shift occurs from lens swelling due to accumulation of sorbitol 1 On the other hand ,hyperopic shift occurs when there is a significant reduction of the concentration of glucose in the aqueous humor 1 1 Feldman- Billard S, Dupas B. Eye disorders other than diabetic retinopathy in patients with diabetes. Diabetes & Metabolism. 2021 Nov 1;47(6):101279.

14. Refractive instability in diabetes Increased blood glucose level Increase glucose level within lens Sorbitol, converted from excess Intracellular glucose, accumulates within the lens  induces an influx of water from the aqueous humour   Swelling of lens Myopic shift

15. Refractive instability in diabetes Decreased glucose concentration in the aqueous humour transient difference in osmotic pressure between the aqueous humour and crystalline lens  Decrease in refractive index of lens Hypermetropic shift Seen in initial treatment of diabetes

16. Accommodation in diabetes Diabetic eye disease can manifest as a reduced amplitude of accommodation Partly due to changes in lens hydration and the lens capsule   State of hyperglycaemia cause glycogen deposition within the ciliary body, causing a decrease in function   A decrease in accommodative amplitude reported in patients receiving PRP for diabetic retinopathy

17. Cataract in diabetes Senile cataract appear at an early age and progresses rapidly due to increased deposition of AGEs True diabetic cataract  ✔Increased glucose level in aqueous humour   ✔Leads to accumulation of sorbitol in the lens   ✔Large no. of cortical fluid vacuoles develop and later evolve into frank opacities   ✔Appearance of bilateral snowflake like white opacities in the cortex 

18. Diabetic Retinopathy Progressive dysfunction of the retinal vasculature caused by chronic hyperglycemia resulting in structural damage to neural retina Risk factors for DR Duration of diabetes Poor glycaemic control Hypertension  Nephropathy Pregnancy Others ( hyperlipidaemia,anaemia,obesity,smoking )

19. Pathogenesis Hyperglycemia Elevated blood glucose: Sorbitol trapped intracellulary (Osmotic forces drag water inwards cause edema) Accumulation of Advanced Glycation End Products( toxic) Free Radical Production (Oxidative damage) Cellular damage Endothelial cell loss(Macrophage & Complement activation) Pericyte loss Thickening of basement membrane

20. Pathogenesis Haemotological & Biochemical changes Platelet adhesiveness Increase blood viscosity RBC deformation Dyslipidemia Cellular and Biochemical changes lead to Weakened vessel wall (Microaneurysms) Breakdown of BRB ( Edema , Exudates, Haemorrhages) Collateral shunts (IRMAs)

21. Pathogenesis Retinal Ischemia Increased proangiogenic factors : VEGF, HGF, PDGF Decreased antiangiogenic factors: Angiostatin, Endostatin Neovascularization NVD or NVE (Progression) Along retina progress : Formation of epiretinal membrane Into Vitreous due to Contraction : Rupture(Vitreous Haemorrhage) or Traction(Posterior Vitreous Detachment)

22. Early Treatment Diabetic Retinopathy Study(ETDRS) Classification Non Proliferative Diabetic Retinopathy (NPDR) Signs Very Mild NPDR Microaneurysms only Mild NPDR Any or all of: microaneurysms, retinal haemorrhages , exudates, cotton wool spots, up to the level of moderate NPDR. No IRMA or significant beading  Moderate NPDR Severe retinal haemorrhages (about 20 medium–large per quadrant) in 1–3 quadrants or mild IRMA  • Significant venous beading can be present in no more than 1 quadrant   • Cotton wool spots commonly present  Severe NPDR The 4–2–1 rule; one or more of:   • Severe haemorrhages in all 4 quadrants  • Significant venous beading in 2 or more quadrants  • Moderate IRMA in 1 or more quadrants  Very Severe NPDR Two or more of the criteria for severe NPDR 

23. Early Treatment Diabetic Retinopathy Study(ETDRS) Classification Proliferative Diabetic Retinopathy (PDR) Signs Mild-moderate PDR   New vessels on the disc (NVD) or new vessels elsewhere (NVE), but extent Insufficient to meet the high-risk criteria  High risk PDR   NVD greater than about 1/3 disc area  Any NVD with vitreous haemorrhage   NVE greater than 1/2 disc area with vitreous haemorrhage   Advanced diabetic eye disease   Hemorrhage(preretinal, intragel or both), Tractional RD, Rubeosis Iridis  

24. Non Proliferative diabetic retinopathy Retinal microvascular changes: Confined to Retina not beyond ILM Microanneurysms   Retinal haemorrhages Lipid exudates Cotton-wool spots Venous caliber changes IRMA Clinically Significant Macular edema

25. Microaneurysms First ophthalmoscopically detectable in diabetic retinopathy and considered the hallmark of NPDR Localized outpouchings of the capillary wall formed either by focal dilatation of capillary wall where pericytes are absent or by fusion of a capillary loop Seen in inner nuclear layer

26. Retinal Haemorrhages Retinal nerve fibre layer (flame shaped) haemorrhages arise from pre-capillary arterioles Intraretinal haemorrhages arise from venous end of capillaries Located in compact middle layers of retina with resultant red 'dot/blot' configuration Extent of involvement is a significant marker of progression to PDR

27. Lipid exudates Waxy yellow lesions with relatively distinct margins arranged in clumps at the posterior pole ,surrounding leaking microanneurysms Composed of lipoprotein and lipid filled macrophages located mainly within the outer plexiform layer

28. Cotton-wool spots Small fluffy whitish superficial lesions that obscure underlying blood vessels Result from ischaemic disruption of nerve axons, swollen ends known as cystoid bodies in nerve fibre layer

29. Venous changes Consists of generalized dilatation and tortuosity Venous looping Venous beading(focal narrowing) Sausage like segmentation

30. Intraretinal microvascular abnormalities General term used to describe the overall pathologic changes in the capillary bed Dilated tortuous telangiectatic channels between arterioles and venules Intraretinal neovascularization Powerful predictor of developing PDR

31. Severe NPDR The 4–2–1 rule; one or more of:  1. Severe haemorrhages in all 4 quadrants  2. Significant venous beading in 2 or more quadrants  3. Moderate IRMA in 1 or more quadrants  Presence of any one of the above = Severe NPDR Presence of two of the above = Very Severe NPDR

32. Diabetic Maculopathy Diabetic maculopathy (foveal edema , exudates or ischaemia) the most common cause of visual impairment in diabetic patients Focal exudative maculopathy Diffuse exudative maculopathy Ischaemic maculopathy Mixed maculopathy Microaneurysms,  Haemorrhages,   Well circumscribed   macular  edema ,  hard exudates in circinate pattern Focal leakage Diffuse retinal edema   Thickening at posterior pole Few hard exudates Diffuse leakage Occurs due to microvascular blockage   Retinal non perfusion and ischaemia  Marked visual loss   Combined features of exudative and ischaemic maculopathy seen  

33. Clinically Significant Macular edema Retinal edema within 500μm of the center of the macula   Hard exudates within 500μm of the center of the macula, if associated with retinal thickening (which may be outside the 500μm)   Retinal edema one disc area (1500μm) or larger, any part of which is within one disc diameter from the center of the macula  

34. Proliferative Retinopathy Characterized by development of new vessels (neovascularization)   from the surface of retina or optic disc as a result of retinal ischemia Most commonly seen at posterior pole New vessels at the disc (NVD) - neovascularization on or within one disc diameter of optic nerve head New vessels elsewhere (NVE) - neovascularization further away from the disc

35. Vitreous Haemorrhage New vessels are often adherent to the posterior hyaloid Posterior vitreous detachment occurs causing new vessels to bleed Blood becomes trapped between retina and posterior hyaloid Pre retinal/ subhyaloid space Classic “boat like configuration”

36. Tractional Retinal Detachment As NVD and NVE progress, fibrous proliferations develop that are adherent to the posterior vitreous face As the vitreous gel contracts with PVD may cause tractional retinal detachment

37. Advanced diabetic eye disease End result of uncontrolled proliferative diabetic retinopathy Marked by complications such as : Persistent dense vitreous haemorrhage Tractional retinal detachment Neovascular glaucoma associated with the formation of blood vessels on the iris (rubeosis iridis)

38. Diabetic papillopathy Diabetic papillopathy is an uncommon ocular manifestation of diabetes mellitus (DM) The underlying pathogenesis is unclear but it maybe the result of small vessel disease Presentation is unilateral or bilateral with hyperemic , swollen disc with disc telengectasia   Must be distinguished from papilledema or other etiologies of optic disc swelling.

39. Diabetic neuropathy Common cause of isolated ocular motor nerve palsy, due to interference with the microvascular blood supply to nerve Third nerve palsy - an isolated pupil sparing, painful Sixth nerve palsy fairly common Fourth nerve palsy may occur Sudden onset of diplopia and painful muscle paralysis assosciated with homolateral headache and eyeache

40. Visual implications of diabetic retinopathy and diabetic maculopathy 1. Visual acuity No effect in very mild and mild NPDR   Central visual acuity may be compromised due to maculopathy   Vision loss secondary to residual effects from vitreous haemorrhage, preretinal haemorrhage, or traction retinal    detachment   Reduced vision in dim light, secondary to retinal ischemia or   p anretinal laser photocoagulation  

41. Visual implications of diabetic retinopathy and diabetic maculopathy 2. Visual field Central scotoma related to macular haemorrhages and macular edema   Peripheral visual field defects associated with large retinal or preretinal haemorrhages, vitreous haemorrhages, and/or areas of fibrous or neovascular lesions in the retina and vitreous   Arcuate scotoma associated with lesions of retinitis  proliferans in contact with the optic disc.  

42. Visual implications of diabetic retinopathy and diabetic maculopathy   3. Color vision Studies report that colour discrimination is abnormal in patients with diabetes even before the onset of retinopathy 1 Tritan-like defect was prominent in diabetic patients which increased in magnitude with increasing severity of macular edema 2 1 Detection of colour vision abnormalities in uncomplicated type 1 diabetic patients with angiographically normal retinas. K J Hardy, J Lipton, M O Scase , D H Foster and J H Scarpello; British Journal of Ophthalmology 1992 2 Impaired color vision associated with diabetic retinopathy: Early Treatment Diabetic Retinopathy Study Report No. 15 1 Donald S Fong , MD, MPH a ,  b , ,  , Franca B Barton , MS c ,  George H Bresnick , MD, MPA d , Early Treatment Diabetic Retinopathy Study Research Group

43. Visual implications of diabetic retinopathy and diabetic maculopathy​   4. Contrast sensitivity A study by Safi et al.(2017) showed patients with diabetes(without any clinical signs of retinopathy) exhibited a uniform loss in CS at different special frequencies like 3, 6, 12, and 18 cycles/degree 1 More sensitive tool to detect early retinal changes and distinguish different diabetic subgroups 1 Safi S., Rahimi A., Raeesi A., Safi H., Amiri M.A., Malek M. Contrast sensitivity to spatial gratings in moderate and dim light conditions in patients with diabetes in the absence of diabetic retinopathy. BMJ Open Diabetes Res. Care. 2017;5:1–9.

44. Visual implications of diabetic retinopathy and diabetic maculopathy ​     5. Glare sensitivity Glare sensitivity is shown to progressively increase throughout the range from normal to advanced stages of diabetic eye disease However, glare sensitivity was found to be greater in those diabetic patients who had received laser treatment 1 1 Contrast and glare sensitivity in diabetic patients with and without pan-retinal photocoagulation S.W Mackie , G Walsh . Ophthalmic and Physiological Optics Volume 18, Issue 2 , March 1998

45. Diabetes and low vision   Visually impaired diabetics have specific needs to be addressed in the low vision examination :  ⮚ to see to fill insulin syringes and take oral medications.  ⮚ to see to test their blood sugar.  ⮚ to read labels on food containers to control their intake of carbohydrates.  ⮚ glare and contrast problem  Specific low vision devices for diabetic patients like glucose monitor aids, insulin syringe aids, CPF lenses can be considered. 

46. Summary Ocular manifestations of Diabetes mellitus are: Tear film: Dry eye syndrome Lids: Recurrent styes and xanthelasma Conjunctiva: Sub conjunctival haemorrhage Cornea: Decreased corneal sensitivity, Neurotropic keratopathy , Delayed epithelial healing Iris: Rubeosis Iridis (Neovascularization) Lens: Snowstorm cataract, Early maturation of senile cataract

47. Summary Ocular manifestations of Diabetes mellitus are: Vitreous: Vitreous haemorrhage Retina: Diabetic retinopathy, Diabetic maculopathy Optic nerve: Optic neuritis, Diabetic papillopathy Extraocular muscles: Ophthalmoplegia due to diabetic neuropathy Changes in refraction: Hypermetropic in hypoglycemia , Myopic in hyperglycemia and decreased accommodation

48. References Nentwich MM, Ulbig MW. Diabetic retinopathy-ocular complications of diabetes mellitus. World journal of diabetes. 2015 Apr 4