Diabetic Retinopathy I, II, III, and IV

A patient can have regressed/inactive PDR in which you can no longer see blood flowing through vessels and fibrous tissue is present. We are worried about what with these patients?

Tractional RD

The Subthreshold photocogulation works well because it divides laser emission into a "____" of short, repetitive phases which allows for heat _______.

Train (Some on and some off times) Dissipation

T/F. After 6 weeks patient may see increase in vitreoretinal traction due to contracture of fibrovascular tissue.

True

T/F. Anti-VEGF agents are generally only beneficial as an adjunct to PPV by reducing intraoperative bleeding because their results are temporary (expedite resolution of vitreous hemorrhage).

True

T/F. Location of retinal thickening relative to foveal center is important for diagnosis of clinically significant macular edema.

True

T/F. Macular Edema can occur at any stage of diabetic retinopathy.

True

T/F. More than 1 treatment of macular photocoagulation may be necessary.

True

T/F. PPV may be useful when vitreomacular traction exists, DME is diffuse, and other treatments fail but the exact role of vitrectomy is unknown.

True

T/F. Patients with DME demonstrate increased levels of vitreous VEGF and decreased levels of PEDF.

True

T/F. Proliferative diabetic retinopathy may be active or inactive.

True

T/F. RD from DR maybe tractional or combination of tractional and rhegmatogenous.

True

T/F. Sub-tenon's injection of triamcinolone, intravitreal injection of triamcinilone and intravitreal sustained release implants are all possible treatments of DME but are not used very often at all because of HUGE SE list.

True

T/F. The risk of diabetic retinopathy increases with DURATION of the disease? (******)

True

T/F. You should REFER ALL PATIENTS WITH CSME?

True

T/F. You should refer all patients WITH ANY AMOUNT OF NVI or NVA for PRP (even though it is NOT a HRC).

True

What two patients benefit most from early vitrectomy?

Type 1 DM High Risk PDR (very severe)

A 22year old patient comes into your office and claims to have been diagnosed with diabetes at a young age, for which she takes insulin. According to these characteristics what type of diabetes does she likely have?

Type 1 Diabetes

A 55yo obese male patient comes into your office claiming to have been recently diagnosed with a type of diabetes for which he takes medicine and diet and exercise. According to these characteristics which type of diabetes does he likely have?

Type 2

Diabetic Macular Edema: Is it more common in type 2 or type 1?

Type 2

This study used HTN and newly diagnosed T2DM to determine the effect of tight glycemic control and HTN control on DR in patients with T2DM.

United Kingdom Prospective Diabetes Study (UKPDS)

Diabetic retinopathy can also result in an imbalance in angiogenic and antiangiogenic factors. This angiogenic factor shows INCREASED LEVELS in DR and promotes neovascularization and increased vascular permiability. It is upregulated by what?

VEGF Hypoxia

This stage of NPDR is characterized by having TWO OR MORE criteria of the 4-2-1 rule. What is the risk that a patient will develop HIGH RISK PDR requiring treatment in one year? (******) Refer pt. for consult.

Very Severe NPDR. 45%

What are two causes of severe vision loss from PDR?

Vitreous/Preretinal Hemorrhage Tractional RD/Combined RD/Rheg RD

What was the conclusion of the Diabetic Control and Complications Trial?

Tight control of type 1 diabetes significantly reduces the development and progression of DR and nephropathy and neuropathy.

The Ranibizumab for Edema of the Macula in Diabetes 2 (READ-2) Trial compared lucentis to photocoagulation and a combo of the two. What were the three conclusions for this trial?

1. Best treatment is combination of lucentis and photocoagulation 2. Lucentis increased visual improvement and photocoagulation decreased number of injections needed 3. Lucentis reduced ME early and photocoagulation maintained reduction in ME

What was the concolusion of the Epidemiology of Diabetic Interventions and Complications study (EDIC)?

Tight glycemic control early in Type 1 DM persists for 10 years even if tight control is not maintained.

What are six risks factors for developing Type 2 Diabetes?

1. Increasing Age 2. Overweight 3. Family h/o of diabetes 4. Other systemic conditions 5. High risk ethnic group 6. Physically inactive

What were the three conclusions/recommendations of the ETDRS? (*******)

1. Macular photocoagulation for macular edema decreased risk of MVL and should be considered for all eyes with CSME (mild/moderate/severe/PDR) 2. Patients who show early signs of DME but not CSME should be seen at 4 month intervals 3. Consider repeat treatments when CSME persists (4 month intervals)

What are four things that you should tell your patient about PRP?

1. May need to re-treat 2. Completed over several sessions 3. Painful 4. Vision may worsen after treatment

What are four advantages to subthreshold photocoagulation?

1. Microscopic, isolated RPE damage 2. Decreases collateral damage and spares photoreceptors 3. Overlapping may extend into noninvolved areas 4. Frequent re-treatement can be done without fear of scarring

High-Risk PDR has three criteria including high risk characteristics, what are they? (*******) During this stage the risk of vision loss outweighs the risk of treatment of PRP side effects. You must refer these patients for tx.

1. Neo on or within 1DD of the disk greater than or equal to 1/4-1/3 of disc area WITH OR WITHOUT VH/PRH. (10A) 2. Any size NVD associated with vitreous/preretinal hemorrhage 3. NVE at least 1/2 disc diameter in size with preretinal/vitreous hemorrhage.

The third part of the ETDRS study asked: when should PRP be done? What were the four conclusions of this study?

1. Provided careful follow-up is done it is safe to defer patients until retinopathy becomes high-risk PDR 2. Type 2 benefit more from early PRP 3. Mild or moderate NPDR should not be treated with PRP 4. Patients with high risk PDR should be considered for treatment with PRP

What are two disadvantages of subthreshold photocoagulation?

1. Takes longer to work, retreatment often needed 2. Don't know where patient has already been treated

Give the three characteristics NECESSARY to be classified as CSME? (one out of 3 needed)

1. Thickening of retina at or within 500 microns of the center of the macula 2. Hard exudates at or within 500 microns of the macula with associated thickening in adjacent retina 3. Retinal thickening 1DD in size or larger any part of which is within 1DD of the macula center.

500 microns equals what DD?

1/3

In a patient with pre-existing DM without DR ___-______% progress risk of developing DR. If a patient begins pregnancy with NPDR their chance of progressing to PDR is ____-____%

10-26% 22-40%

When should you follow-up with a patient with NPDR?

3 months after consult

Do tell your patient about the rule of threes....which is?

30% of patients left untreated lose 3 lines of vision in 3 years

What is the risk for developing PDR in 1 year with a patient with Severe NPDR? 15-20% of high risk PDR in 1 year.

52%

PRP Post-Op: usually see regression of neo after ____ weeks. What three things define this regression?

6*** less defined vessels, vessels no longer filled with blood, fibrovascular scar tissue

What is the followup for a patient with mild NPDR?

9 to 12 months (only 5% risk of developing PDR in 1 year)

If a VH is so dense that you cannot see the retina you must do what?

B-scan

The second portion of the ETDR study questioned the use of aspirin in patients with DR. What were the three results?

ASA does not affect DR or visual outcome ASA does not increase risk of VH/PRH ASA DOES reduce CVD mortality and morbitity

Consider a PPV if: patient has ______, ____ PDR with ____ vision; diffuse DME with vitreomacular traction, dense, ____ (>____ months) VH; _____ VH; if VH is severe or bilateral; Dense preretinal hemorrhage covers ____; _____ segment neo with associated VH preventing PRP; red bloood cell induced glaucoma; _____ RD threatening macula, combined tractional and rheg RD.

Acute, severe, useful nonclearing, 3 recurrent macula anterior tractional

These are proinflammatory mediators that can bind to endothelial cells causing damage.

Advanced glycation end products

In what two ethnic populations is diabetes mellitus most significant?

African Americans Hispanic Americans

LP MOA: Re-establishes balance between what? How?

Angiogenic and Antiangiogenic factors Increases PEDF Decreases VEGF

Type 1 Diabetes: ______ mediated destruction of beta cells. Is there any insulin secretion? Usually begin taking insulin when? Greater tendency towards ____.

Autoimmune No, complete absence of insulin secretion At time of diagnosis Ketoacidosis

This refers to the ability of the retina vasculature to adjust vessel diameter in order to maintain constant blood flow despite changes in IOP, perfusion pressure ,and blood oxygen levels.

Autoregulation

LP MOA: May also help in restoring ______ retinal arteriolar constriction decreasing what two things?

Autoregulatory Downstream capillary hydrostatic pressure Fluid Leakage

This says that the faster a fluid flows the less pressure it exerts sideways.

Bernoulli effect

Pericytes: Line capillary walls and surround and suppor the retinal ___ _____ cells. They provide vascular stability and control endothelial proliferation.

Capillary endothelial

Eyes with ____ RD are at higher risk for anterior seg neo.

Chronic

In the ETDRS Macular photocoagulation study FA was used to identify treatable lesions located between 500 microns and 2DD from foveola (______ patients). Tx. reduced occurance of MLV by ______ to _____ % in eyes with CSME. Tx was less effective at ____ vision than preventing vision loss.

Chronic 50-70 Improving

The goal of this study was to determine the effect of tight glycemic control on DR in patients with TYPE 1 DIABETES.

DCCT (Diabetic Control and Complications Trial)

A state of absolute or relative insulin deficiency, characterized by hyperglycemia and the risk of microvascuar and macrovascular complications.

Diabetes Mellitus

What is the leading cause of blindness in ages 20-64 in the U.S? (working class?)

Diabetic Retinopathy

This was a large RCT designed to evaluate the risks and benefits of performing a early vitrectomy in eyes with advanced, active PDR and useful vision. What were the two conclusions of this study?

Diabetic Retinopathy Vitrectomy Study (DRVS) 1. Severe, active PDR and useful vision early vitrectomy can improve prognosis for good vision without increasing risk of poor vision and should be considered 2. Vitrectomy is not an ALTERNATIVE for PRP bt shoul dbe used when PRP fails or when VH is present.

In this classification of diabetic retinoapthy it is characterized by neovascularization or extraretinal fibrovascular tissue and occurs on top of retina.

Proliferative diabetic retinopathy

In Type 2 Diabetes what is the most common cause of blindness?

Diabetic macular edema

This type of DME is characterized by widespread retinal capillary leakage and extensive breakdown of inner blood retinal barrier.

Diffuse DME

What are two clinical features associated with tx failure for DME?

Diffuse ME Macular ischemia

The ETDR study defined treatable lesions as what three things?

Discrete points of hyperfluorescence or leakage Arease of diffuse leakage within the retina Retinal avascular zones

Risk factors for Diabetic retinopathy include: longer _____ of DM, poor glycemic control, uncontrolled systemic _______, hyperlipidemia, _______, proteinuria, vasculitis, vitamin D deficiency, ______, ______ surgery, and sleep apnea.

Duration Hypertension Pregnancy Smoking Cataract

This was a long-term observational study of DCCT cohort asking HOW LONG does benefit of early tight glycemic control last?

EDIC: Epidemiology of Diabetic Interventions and Complications

This study asked the following three things: Does macular photocoagulation reduce risk of MVL in patients with DME? Does aspirin alter DR or cause VH/PH? When should PRP be done?

ETDRS (Early Treatment Diabetic Retinopathy Study)

What study said that the benefit of macular photocoagulation outweighs the risk in eyes with CSME?

ETDRS (Early Treatment Diabetic Retinopathy Study)

This stage of PDR does not meet high-risk criteria. Should you treat this patient? What SHOULD you do for this patient?

Early/Low-Risk PDR No, wait for high risk PDR Refer for consult

What are four major complications of PPV (****)?

Endophthalmitis Cataracts Glaucoma RD

T/F. Metabolic changes that occur in diabetes cannot occur in the vitreous.

False, metabolic changes that occur in diabetes CAN OCCUR IN VITREOUS ITSELF.

Prediabetes is considered when the fasting glucose is what? when the 2-hr OGTT is what? After ten years, 1/3 of these patients will have developed type 2 diabetes.

Fasting: 100-125 mg/dl 2-hr OGTT: 140-199 mg/dl

This type of DME is characterized by areas of focal fluorescein angiography leakage from MA, IRMA, and other capillary lesions. It may also present with circinate ring of exudates.

Focal DME

According to ETDRS what type of laser tx should be used on patents with areas of discrete leakage?

Focal Laser

According to ETDRS what type of laser tx should be used on patients with diffuse leakage OR nonperfusion?

Grid Laser Tx

When controlling systemic conditions in patients with diabetes we want HBA1C to be less than? Blood pressure less than? Total cholesterol? Triglycerides? LDL? HDL?

HBA1C: <6.5% BP: <130/80mmHg Cholesterol: <200mg/dl Trig: <150mg/dl LDL: <100 mg/dl HDL: >50 mg/dl

Laser Photocoagulation: A threshold burn creates a ____ _____ that spread outward adjacently from the origin in the burn site of RPE/Choroid. The endpoint is "__-___" colored retina signaling neurosensory retina has been reached.

Heat Wave Greyish-White

LP MOA: Reduction in retinal _____ drive by destruction of metabolically active _______. PRP decreases ____ consumption of retina so oxygen from choroidal circulaton can now diffuse and compensate for reduced blood supply. Summary: Burn is so hot we destroy photoreceptors thus reducing oxygen demand. O2 can diffuse through scar into inner retina and reestablish balance. (********)

Hypoxic Photoreceptors Oxygen

What was the main conclusion of the diabetic retinopathy study?

Prompt PRP should be done in patients with high risk PDR.

Hyperglycemia increases activation of this which increases vascular permeability and promotes development of neo.

Protein Kinase C

Hyperglycemia ________ retinal blood flow but IMPAIRED retinal autoregulation _______ autoregulatory arteriolar constriction which results in what? This increased blood flow results in shear stress and damage to vessels.

Increases Inhibits Elevated capillary hydrostatic pressure

Aldose Reductase mediated damage contributes to what for structural abnormalities in the retinal capillary system?

Loss of Pericytes Basement Membrane Thickening Endothelial Cell Dysfunction Breakdown of inner blood retinal barrier

What are three commercially available anti-VEGF agents?

Lucentis, Avastin, and Macugen

This is the most common cause of decreased vision in DR (*********).

Macular Edema

NPDR can decrease vision in what two ways?

Macular Ischemia Macular Edema

In a patient with severe NPDR what two things should you do?

Medical Work-up Refer for retinal consult

Type 2 Diabetes: Is the majority of diabetes cases. Usually begin taking ____ first and then insulin. Is associated with what other systemic disease in 58% of cases? It is cause by insulin _____ with relative insulin deficiency.

Medications Hypertension Resistance

This is prediabetes or DM combined with one or more of the following: HTN, High Triglycerides, Low HDL Cholesterol, and Central obesity.

Metabolic Syndrome (Syndrome X)

This is the first visible lesion in DR. (******?

Microaneurysms

Pericyte loss permits thin walled dialations called what? The loss of these cells also promotes what?

Microaneurysms Endothelial cell proliferation

This NPDR stage is characterized by at least ONE microaneurysms (but only microaneurysms). There are no hemes, CWS, etc. Do you treat this patient? What should you do?

Mild NPDR No Educate your patient on compliance of medication and diet

This NPDR stage is characterized by more than just microaneurysms but less than severe NPDR. May see CWS, dot/blot, venous beading, or mild IRMA. There is a 12-27% risk of progressing to PDR in 1 year and 33% of progressing to high-risk PDR in 5 years. When should you follow up with this patient?

Moderate NPDR 6 months

In the DVRS study with very severe PDR, early vitrectomy increased chance of 20/40 or better vision, but what hppened in patients with the least severe PDR?

NLP risk actually increased

A patient has exuduates....does this mean that they have DME?

NO! Just because a patient has exudates DOES NOT MEAN there is DME (exudates will increase after tx, however)

The most common microvascular complications of DM at 40% is what? What are three other complications?

Neuropathy Nephropathy CVD Diabetic retinopathy (25-50%)

PRP Complications include: long-term VA decrease (10%), generalized visual field constriction, decreased _____ vision, elevated DA thresholds, increased ______, _______ of DME (*****), optic atrophy, accidental foveal urn, temporary loss of ____ _ and ______, patient subjective difficulty (color defect, judging distance, avoiding obstacles, adjusting lighting).

Night Glare Worsening Corneal Sensation Accommodation

Do you need FA to diagnose DME? When would you do FA?

No!!!! Prior to treatment with photocoagulation

In this classification of diabetic retinopathy is characterized by the absence of neo and changes ONLY TO THE RETINA (do not extend past ILM).

Nonproliferative diabetic retinopathy

This angiogenic inhibitor is DECREASED in PDR but levels increase after photocoagulation tx.

PEDF

You should refer all patients with acute preretinal/VH to a retinal specialist to have what done?

PRP

What are three general methods to treat PDR?

PRP Anti-VEGF PPV (last resort)

What were the two main results of the diabetic retinopathy study?

PRP reduces risk of SVL by >50% Risk of developing SVL > risk of PRP in eyes with HRC

What are two ways (in general) to treat preretinal/vitreous hemorrhage?

PRP, PPV

What are the first cells damaged in DR?

Pericytes

Aldose reductase is an enzyme found in what two places?

Pericytes The Lens

This is protein denaturation induced via absorption of radiant energy that is converted to HEAT by ocular chromophores (targets melanin of RPE and choroidal melanocytes).

Photocoagulation

Aldose Reductase Mediated Damage: In the ______ pathway AR converts excessive glucose to alcohols, mainly _____. This alcohol cannot easily diffuse out of pericytes so it creates an increased ______ _____ leading to ______ and damage.

Polyol Pathway Sorbitol Osmotic gradient Swelling

In Type 1 Diabetes what is the most common cause of blindness?

Proliferative diabetic retinopathy

Side effects of photocoagulation for CSME include progressively enlarging _______ (300%), _____ scotoma (100% of patients), tritan color defects, and neovascularization.

Retinal Scar Paracentral

In a patient with RD you should refer them immediately. Which type of RD is more concerning to us?

Rhegmatogenous

Other complications of DM: decreased corneal _____, RCE, OAG, increased risk of ____, NAION, diabetic papillopathy, CN palsy, neuropathy, etc.

Sensitivity Cataracts

This NPDR stage is characterized by the 4-2-1 rule. What is the 4-2-1 rule?

Severe NPDR Greater than or equal to 4 quadrants of severe retinal heme (2A) Greater than or equal to 2 quadrants of venous beading (6B) Greater than or equal to 1 quardrant of prominent IRMA (8A)

Diabetic Macular Edema most commonly occurs in what type/stage of DR?

Severe NPDR (77%)

What are four things that you should tell your patient to do if vitreous hemorrhage is present?

Sleep sitting up Don't lift weights Do not bend below waste Do not do anything that can cause traumma

This type of photocoagulation is one that uses a 810 nm micropulse diode laser with low intensity in high density area. It does NOT produce visible intraretinal damage or scarring during or after treatment.

Subthreshold Micropulse Diode Laser Photocoagulation

What three pieces of information lead us to believe a diagnosis of DM?

Symptoms with casual plasma glucose >200mg/dl Fasting plasma glucose >126mg/dl 2-hr plasma glucose >200mg/dl during OGTT

You should consider treating severe or very severe NPDR or low-risk PDR if which of the following features are present? (x5)

T2DM T1DM long duration Rapid progression Cataract surgery Noncompliance

What should you not tell your patient about macular photocoagulation?

That it will improve vision, it will not. It will only sustain the vision you have (hopefully)

This study was done to determine whether PRP reduced rate of SVL in patients with PDR or Severe NPDR. It compared immediate PRP to observation.

The diabetic retinopathy study

What was the conclusion of the UKPDS study?

Tight HTN control decreases progression of DR, vision loss, and other systemic microvascular complications.

How do we diagnose diabetic macular edema?

With biomicrscopy we should see an elevated area with decreased transparency.