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 instability3
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 cornea1
• 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 defect2
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 control1
• In case of increased blood glucose level ,myopic shift occurs from lens swelling
due to accumulation of sorbitol1
• 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 panretinal 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 edema2
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. 151 Donald S Fong, MD, MPHa, b, , , Franca B Barton, MSc, George H Bresnick, MD, MPAd, 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 treatment1
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