Hypertension: Types, Causes & Retinopathy

Hypertension Types

• Essential hypertension accounts for 90-95% of cases and has no identifiable underlying cause.
• Secondary hypertension accounts for 5-10% of cases and is linked to underlying issues.

Causes of Secondary Hypertension

• Sleep apnea, characterized by airway collapse and sympathetic system activation during sleep.
• Certain medications like steroids, decongestants, stimulants, and birth control.
• Endocrine disorders such as Cushing’s disease, hypothyroidism, and hyperthyroidism.
• Renal disease.
• Illicit drug use, including cocaine, narcotics, and methamphetamine.

Hypertensive Retinopathy: Vasoconstrictive Phase

• Involves constriction of precapillary arterioles, mainly in second and third-order arterioles.
• Diffuse constriction affects the entire vessel uniformly, while focal constriction varies in size.
• Vasoconstriction is an early and reversible sign, especially with BP control.
• Autoregulation optimizes retinal blood flow.

Hypertensive Retinopathy: Vasosclerotic Phase

• Thickening and hardening of artery walls, leading to decreased blood flow.
• Atherosclerosis affects large/medium vessels while arteriosclerosis affects small/arteriolar vessels.
• Hypertension speeds up sclerotic changes and causes irreversible vascular damage.
• Arteriolar wall damage and thickening occur to protect against vasoconstriction.
• Broadening and dimming of the light reflex appear.
• Copper wiring turns the light reflex reddish-brown; silver wiring obscures the blood column.
• A/V nicking (Gunn’s sign) results from compression of the underlying venule.
• Salus sign is a typical combination finding.

Hypertensive Retinopathy: Exudative Phase

• Occurs with chronic HTN or abrupt BP changes.
• Compromised tight junctions in retinal vessels disrupt the blood-retinal barrier.
• Flame hemorrhages occur in the nerve fiber layer (NFL).
• Cotton-wool spots, are microinfarctions in the NFL due to capillary closure and ischemia.
• Hard exudates, located in the outer plexiform layer (OPL), result from pre-capillary arteriole leakage.

Malignant Hypertension

• Presents with high pressure, retinal hemorrhages, exudates, cotton-wool spots, or optic nerve swelling.
• Diastolic BP is usually above 120 mmHg.
• Hypertensive crisis or malignant hypertension can lead to optic disc edema (papilledema) from hypertensive encephalopathy.

Hypertensive Urgency vs. Emergency

• Hypertensive Urgency: Severe BP elevation (systolic >180 and/or diastolic >120) without retinopathy or CNS changes; requires referral.
• Hypertensive Emergency: Severe BP elevation (systolic >180 and/or diastolic >120) with retinopathy or CNS changes.

Grading Classifications

• Keith Wagner Barker: Classifies retinopathy from slight arteriolar constriction to papilledema, exudates, and hemorrhages.
• Scheie: Stages retinopathy, and also arteriolar sclerosis; ranges from no abnormalities to severe changes like edema and disc swelling.
• ICD code H35.013 is used for changes in retinal vasculature appearance, bilateral, when the patient does not have HTN.

Hypertensive Choroidopathy

• Choroidal blood vessels lack autoregulation.
• Elschnig spots appear in young patients with acute hypertension and renal dysfunction, indicating RPE changes from choriocapillaris non-perfusion.
• Siegrist streaks are linear hyperpigmented streaks along choroidal vessels due to choroidal vascular sclerosis.
• Serous and RPE detachments can occur.

Complications of Vasosclerotic Phase

• Vein and artery occlusions
• Retinal macroaneurysms, particularly in elderly patients.

Differentials

• Chronic differentials include diabetic retinopathy and retinal venous obstruction.
• Acute differentials include bilateral bullous central serous chorioretinopathy.

Diabetic Retinopathy (DR) Statistics

• Leading cause of blindness in working-age adults.
• 11.7% of US adults with diabetes had vision disability in 2018.
• Nearly half of all diabetic patients will develop DR by 2030.

General DR Information

• DR is a common complication of both type 1 and type 2 diabetes.
• It is considered a microvascular disease of the retina, but retinal neurodegeneration may be an early event.
• Type 1: 5-10% of DM population, immunological cause, typically diagnosed before age 30.
• Type 2: 90-95% of DM population, adult-onset, slow progression, involves insulin resistance.
• Gestational DM: Occurs in 2-10% of pregnancies, mother and baby at higher risk of developing type 2 diabetes.
• Prediabetes: Glucose levels are higher than normal but not high enough for diabetes diagnosis.

Risk Factors for DM/DR

• Family history of diabetes/DR
• Hypertension and cardiovascular disease
• Abnormal blood lipid levels
• Prediabetes, gestational diabetes
• Obesity and longer DM duration
• Older age (>45)
• Smoking and physical inactivity
• Race (African Americans, Hispanics)

Diabetes and the Eye

• DR can lead to high blood pressure, high cholesterol, heart disease, stroke, kidney failure, amputation, and early death.
• Nearly 100% of Type 1 and 60% of type 2 diabetes patients will develop DR
• Risk of DM microvascular complications is reduced by 40% for every 1% absolute decrease in A1c level.
• Risk of diabetes-related microvascular complications is reduced by 12% for every 10 mmHg reduction in systolic blood pressure in hypertensive patients.
• Early detection and treatment can reduce the risk of DR.
• 60% of type 1 diabetes patients will develop any stage of DR within 10 years; 53% to 84% of type 2 diabetes patients within 19 years.
• Approximately 20% of type 1 and 14-25% of type 2 diabetes patients will develop diabetic macular edema (DME) after 10 years.
• DME is the most common cause of vision loss in diabetes.
• Patients with longer durations of diabetes, higher glycemia levels, greater BMI, higher blood pressure, and nephropathy are at greater risk of vision loss.

DR Stages

• Non-proliferative stages are marked by microaneurysms, hemorrhages, venous dilation, and cotton wool spots.
• Increased vascular permeability leads to retinal thickening (edema) and lipid deposits (hard exudates).
• Clinically Significant Macular Edema (CSME) is retinal thickening and/or hard exudates involving or threatening the macula center.
• As DR progresses, vascular closure results in ischemia.
• Signs of ischemia include venous abnormalities, IRMA, and vascular leakage.
• More advanced PDR is characterized by neovascularization induced by retinal ischemia.
• New vessels are prone to bleed, leading to vitreous hemorrhage (VH).
• Fibrous proliferation may result in epiretinal membrane formation, retinal tears, and retinal detachments (TRD).

Mild Non-Proliferative Diabetic Retinopathy (NPDR)

• Microaneurysms only, without significant retinopathy stages.
• Focal dilations of retinal capillaries, located in the inner nuclear layer (INL).
• Earliest signs.
• 5% probability of mild NPDR progression to PDR in one year.

Moderate NPDR

• Microaneurysms and dot or blot hemorrhages may be present.
• Hard exudates (OPL) and cotton wool spots may be present.
• Mild venous beading and IRMA (shunt from nonperfused to perfused areas) may be seen.
• 12-27% of moderate NPDR cases will develop PDR within one year.

Severe NPDR

• Includes severe microaneurysms and dot or blot hemorrhages in all four retinal quadrants.
• Definite venous beading in two or more quadrants.
• 50% risk of developing into PDR within one year.

IRMA

• Tortuous dilated capillaries act to supply areas of non-perfusion.
• Does not leak on fluorescein angiography (FA).
• Sign of retinal hypoxia.

Venous Beading

• Reflects increasing retinal ischemia caused by prolonged cycles of hypoxia.
• Appears adjacent to large areas of nonperfusion.
• Strong predictor of the development of PDR.

Very Severe NPDR

• Includes 2 or more criteria of severe NPDR but without neovascularization.
• 75% risk of developing into PDR in 1 year.

Proliferative Diabetic Retinopathy (PDR)

• Neovascularization on the retinal surface, optic nerve, or anterior segment.
• Classified based on risk factors, including the presence and extent of new vessels and vitreous hemorrhage.
• High-risk PDR involves at least one of the following: NVD ≥ ¼ - ⅓ disc area, any NVD with vitreous or pre-retinal hemorrhage, or any NVE with vitreous or pre-retinal hemorrhage.
• Low-risk PDR involves NVD < ¼ without vitreous hemorrhage.

Vitreous Hemorrhage (VH)

• Location may be boat-shaped or within the vitreous body.
• Subhyaloid hemorrhage occurs between the posterior vitreous base and internal limiting membrane.
• Pre-retinal hemorrhage occurs posterior to the internal limiting membrane.

Tractional Retinal Detachment (TRD)

• The most advanced form of diabetic retinal disease.
• Contraction of vitreous or areas of fibrovascular proliferation may lead to RD.

NVI & NVA

• Neovascularization in pupillary border and in the angle can cause secondary glaucoma.
• Vasoproliferative factors from vessels in the back proliferate into the anterior chamber through the aqueous.

Diabetic Macular Edema (DME)

• Intraretinal fluid leaking within the macula, with or without lipid exudate or cystoid changes.
• Frequent cause of vision loss.
• DME is now defined as center-involved (CI-DME) or non-center-involved (NCI-DME).

Clinically Significant Macular Edema (CSME)

• Marked by thickening of the retina at or within 500 um of the center of the macula
• hard exudates at or within 500 um of the center of the macula associated w/ thickening of the adjacent retina
• retinal thickening one disc diameter or larger, part of which is within one disc diameter of the center of the macula.
• The VA is not part of the criteria for defining macular edema

OCTA

• Vitreoretinal interface (VRI) includes data from the internal limiting membrane (ILM) and extends 300 um into the vitreous.
• Superficial retina OCTA includes vascular data from the NFL, GCL, and IPL.
• Deep retina includes vascular data from the inner nuclear and outer plexiform layers.

Care Process Exam

• History, exam, visual acuity and pupils (always PH), slit-lamp biomicroscopy.
• Intraocular pressure, gonio when vessels are apparent in pupillary margin, DFE, pictures.
• Color and red-free fundus photography, OCT, fluorescein angiography (FA), OCT angiography, B-scan ultrasonography.

Management for ODs

• Mild NPDR: Document whether DME/CSME is present; educate patient; follow up in one year if no DME, sooner if A1c is changing rapidly.
• Moderate NPDR: Communicate with PCP; follow up every 3-6 months without DME; refer to a specialist if center-involved DME is present.
• Severe NPDR/very severe NPDR/non-high risk PDR: Referral to a retina specialist is needed within 1-2 weeks.
• High-risk PDR: Referral needed to a retinal specialist within 24-48 hours.

DME Treatment

• Defer if VA is good (20/30 or better) and monitor every 2-4 months.
• Anti-VEGF injections are monthly for 4-6 months, then PRN.
• Anti-VEGF agents like Lucentis, Avastin, Eylea, Vabysmo, Beovu, and Macugen are used.
• Susvimo, a refillable implant, is now approved for DME treatment.
• Focal or grid laser treatment (photocoagulation) is recommended for NCI-DME.

Diabetic Retinopathy/Diabetic Macular Edema Treatment

• Laser MOST effective is the Krypton red because the red wavelength is not absorbed by the xanthopyll in the macula
• The Argon blue IS NOT RECOMMENDED because blue wavelength is highly absorbed by the xanthophyll of the macula and will burn it.
• Indicated for patients with CSME
• Technique: krypton red reduces fluid passage and seals leaking microaneurysms.

Steroids for DME

• Triamcinolone reduces severe progression and extensive macular edema.
• Dexamethasone implant and fluocinolone implant are approved.
• Side effects include cataract progression and elevated IOP.

Treatment in DR

• Panretinal Photocoagulation (PRP) reduces the stimulus to neovascularization in PDR.

Lasers Used in Photocoagulation

• Argon: 488, 514nm (blue and green).
• Krypton: 531, 568, 647nm (green, yellow, red). Best choice is Krypton Red
• Nd: Yag: 532, 1064nm.
• Diode: 620-895nm (750-850nm).
• The most effective lasers for PRP are Krypton and Argon greens for PDR b/c absorbed well by retina.
• Krypton MOST effective if treating vessels directly because it will be highly absorbed from hemoglobin

PRP Technique

• The goal of PRP is to reduce the risk of vision loss.
• ETDRS protocol included 1200 to1600 spots of moderate burns of 0.1 second duration.
• Complications include field restriction, nyctalopia, foveal burn, and macular edema.

Vitrectomy

• Indicated for dense vitreous hemorrhage, traction retinal detachment, macular epiretinal membranes, and severe retinal neovascularization unresponsive to laser.

Differential Diagnosis

• For NPDR: CRVO, ocular ischemic syndrome, HTN retinopathy, and radiation retinopathy.
• For PDR: Neovascular complications of CRAO, CRBO, or BRVO; sickle cell retinopathy. And also sarcoidosis.
• For acute : ocular ischemic syndrome and radiation retinopathy

Sickle Cell Retinopathy

• Hereditary autosomal recessive condition.
• Anomalous cells prevent normal blood flow, increased blood viscosity, hypoxia, venous stasis, acidosis, and inflammation.
• Affects 100,000 individuals in the US.
• Sickle cell retinopathy (SCR) is the most common cause of vision impairment in these individuals.

SCD Variants

• SS (Sickle Cell Anemia): two genes w/ S hemoglobin ( glutamic -> valine x2)
• AS (Sickle Cell Trait): one normal parent (A) & S: glutamic -> valine (carrier state)
• SC (Sickle Cell C Disease): S: valine, C: lysine**
• SThal (Sickle Cell Thalassemia): beta subunit gene = absent/reduced
• HbSC and SThal are associated with more severe ocular disease, yet have far fewer systemic manifestations.

Ocular Findings of Sickle Cell Retinopathy

• Conjunctival sickling sign (capillary vessel segmentation)
• Iris atrophy and neovascularization
• Spontaneous hyphema (DO NOT use CAIS- will promote more sickling)
• Primarily affects peripheral retina.
• Symptoms: Floaters/flashing lights/loss of vision.

Retina Signs

• Thrombotic arteriolar occlusions around the equator.
• Retinal changes can include intraretinal salmon-patch hemorrhages.
• Peripheral arterial occlusion, AV anastomoses
• Sea fan NV, VH , RD

Stages of Retinopathy

• Stage 1: Peripheral arteriolar occlusions and ischemia
• Stage 2: Peripheral arteriovenous anastomoses.
• Stage 3: Sprout of new vessels “sea fan” configuration
• Stage 4: Vitreous Hemorrhage
• Stage 5: Retinal Detachment

Treatment of Sickle Cell Retinopathy

• Anti-VEGF therapy (off-label), vitrectomy and/or repair RD