​Kembara Xtra - Medicine - Age Related Macular Degeneration

​Kembara Xtra - Medicine - Age Related Macular Degeneration 
Age-related macular degeneration (AMD) is the main factor in severe, irreversible vision loss in people over 65.
AMD is categorized as:
- Atrophic/nonexudative alterations in the macular pigment, such as drusen
- Neovascular age-related macular degeneration (nAMD), also known as neovascular/exudative AMD.

Epidemiology 

The nAMD variant is less common in whites and more common in blacks.
Female is the predominant sex; incidence
25% of all participants in the Framingham Eye Study (FES) who were under 52 years old had drusen, according to the study. 5.7% of people had vision loss related to AMD.
Twenty percent of instances of severe vision loss are at the atrophic/nonexudative stage, and eighty percent are at the nAMD stage.
Prevalence
According to a FES survey, 11% of those 65 to 74 years old.
 People aged 75 and older: 27.9%

Pathophysiology and Etiology 

Atrophic/nonexudative alterations to the macula's pigmentation or drusen.
The Bruch's membrane, which serves as the limiting membrane between the RPE and the choroid, and the RPE are separated by hyaline deposits known as drusen.
– The retinal pigment epithelium (RPE), a pigment layer beneath the retina that typically aids in the removal of metabolic byproducts from the retina, may form and accumulate metabolic byproducts as a result of exposure to visible light. The RPE's regular metabolic function is hampered by the excessive accumulation of these metabolic byproducts, which can result in the development of drusen.
– Most people do not advance through the atrophic/nonexudative stage, but those who do have a higher chance of suffering from severe vision loss.
The atrophic stage typically leads to the nAMD stage.
Breaks in Bruch's membrane allow choroidal neovascular membranes (CNVMs) to expand into the sub-RPE area in type 1 neovascularization. This is consistent with occult CNVMs. RPE detachments that are vascularized serous or fibrovascular might result from fluid leakage and hemorrhage.
The CNVM is found in the subretinal space and crosses through the RPE in type 2 neovascularization. usually takes the form of a lacy or grayish-green lesion. This is comparable to traditional CNVM.
Polypoidal choroidal vasculopathy (PCV), a subtype of nAMD, frequently manifests as multiple, recurrent serosanguineous RPE detachments. Type 3 neovascularization, also known as retinal angiomatous proliferations (RAPS), is a neovascularization that develops from the deep capillary plexus of the retina and grows downward toward the RPE. A pigment epithelial detachment (PED) is another name for an RPE detachment. Multiple PEDs, steeply peaked PEDs, notched or multilobulated PEDs, and a hyperreflective ring enclosing an interior hyporeflective lumen underneath a PED are optical coherence tomography (OCT) characteristics of PCV.
25% of AMD cases are genetically predisposed, and complement factor H's Y402H genotype is a key susceptibility gene for the disease. Genetics Specific genotypes can predict the onset of AMD, but they cannot predict the clinical response to anti-vascular endothelial growth factor (anti-VEGF).
Risk factors for AMD include obesity, smoking, Chlamydia pneumoniae infection, family history, excessive sun exposure, blue or light iris color, hyperopia, short stature, and high plasma levels of HDL cholesterol. In white populations, physical activity is linked to a lower risk of both early and late AMD.

Preventative measures include wearing sunglasses to protect eyes from ultraviolet (UV) rays and scheduling regular ophthalmology appointments (every 2 to 4 years for patients 40 to 64 and every 1 to 2 years for patients 65 and older).
DIAGNOSIS HISTORY
Patients typically report central vision distortion. The horizontal or vertical lines in an Amsler grid test may become crooked, misshapen, or absent.

clinical assessment 
Atrophy of the RPE; Atrophic/nonexudative stage; Drusen (small yellowish-white lesions); Hard and soft drusen subtypes;
Geographic atrophy (GA) of the RPE is the term used when a region of absent or attenuated RPE is contiguous.
CNVMs, also known as subretinal neovascularization (SRN), are blood vessels that originate from the choroid and grow beneath the retina in people with nAMD. The vascular layer below the RPE is called the choroid.
- Exudates - Subretinal fluid or hemorrhage
Disciform scar: a stage in which a fibrovascular scar develops.
DISTINCTIVE DIAGNOSIS
Idiopathic SRN, suspected ocular histoplasmosis syndrome, hypertension or diabetes-related retinopathy, central serous chorioretinopathy, and macular neurosensory retinal detachment are all conditions that topiramate may exacerbate.

Investigations in the lab, diagnostic techniques, and other
Fluorescein angiography (FA) distinguishes between nAMD and atrophic AMD.
OCT is helpful in evaluating the existence of subretinal fluid, the level of retinal thickness, and the presence of a PED. Indocyanine green video angiography may detect occult or hidden CNVMs. For assessing AMD, spectral-domain OCT (SD-OCT), swept-source OCT (SSOCT), and OCT angiography (OCTA) are favored OCT modalities of a more recent generation.
- Type 1 (sub-RPE), Type 2 (subretinal), and Type 3 (intraretinal vascular proliferation) of neovascularization are anatomic subtypes that can be seen using OCTA.

Low-vision aids may be useful in management.

First Line of Medicine
Ranibizumab (Lucentis) is an antibody fragment that blocks complete VEGF activity. Up to 40% of patients treated with ranibizumab gained at least three lines of vision after intravitreal injections at a dose of 0.5 mg every four weeks for a year following treatment, and around 95% of patients maintained vision.
– The PrONTO study showed that monthly injections of ranibizumab produced findings that were comparable to those of the MARINA (minimally classic/occult CNVM trial) and ANCHOR (predominantly classic CNVM trial) investigations.
– In a multicenter research, ranibizumab and bevacizumab were compared. Both therapies were successful in stabilizing vision loss, and there was no difference in the visual outcome between the two treatment groups.
In this trial, whether started at enrollment or after a year of monthly treatment, treatment as needed led to less improvement in visual acuity.
Visual advancements made in the first two years were not kept up at five years. 50% of the eyes had vision of 20/40 or better at the 5-year checkup, while 20% had vision of 20/200 or worse.
– In the Comparison of Age-related Macular Degeneration Treatments Trials (CATT), eyes with 50% of the lesion made up of blood had a similar visual prognosis to other treated eyes. Lesions with >50% blood content in nAMD can be treated similarly to those with less or no blood.
– The treat and extend regimen (TER) is frequently employed to ease the burden of treatment. When no CNVM activity is found, patient follow-ups and treatments are then prolonged by intervals of 2 weeks, up to a maximum of 12 weeks, as long as no CNVM activity is found. If an examination reveals any evidence of a recurrence, the duration between exams is reduced by 2 weeks at a time until the disease is deemed to be dormant. The process of interval extension is then continued, with the ultimate maximum interval being 2 weeks shorter than the time frame during which the initial recurrence was seen.
A VEGF receptor spoof called aflibercept (Eylea) binds both VEGF and placental-like growth factor.
- 2 mg intravitreally injected every four weeks for the first 12 weeks, and subsequently every eight weeks.
- After the 12-week fixed dose plan, dosing as needed led to a 5.3-letter improvement in best corrected visual acuity at 52 weeks. Following intravitreal injections (IVIs), prophylactic antibiotic usage may not always be essential.
– Patients who are not responding to ranibizumab or bevacizumab may benefit from this treatment.
– Ranibizumab or aflibercept anti-VEGF therapy has limited efficacy for the full resolution of PEDs.
When moving from a fixed regimen to a PRN method, patients with PED frequently experience inferior outcomes.
All isoforms of VEGF-A are inhibited by the humanized single-chain antibody fragment known as brolucizumab (Beovu). The smallest anti-VEGF antibody is this one.
 Intravitreally injected at a dose of 6 mg once every month for the first three doses, then once every 8 to 12 weeks after that.
The possibility of a 12-week therapy cycle, which would help lessen the frequency of IVIs, exists.
More than half of the eyes treated with brolucizumab continued to get it every 12 weeks.
○ Following the FDA's approval of Beovu, there have been isolated cases of retinal vasculitis and/or retinal vascular occlusion. With the use of brolucizumab, cases of significant vision loss have been documented.

Next Line
Because of its reduced price, bevacizumab (Avastin), a full-length VEGF antibody, is frequently used off-label. It is injected intravitreally at a dose of 1.25 mg.
Angiopoietin-2 and vascular endothelial growth factor A are neutralized by faricimab. The possibility of administering it every 16 weeks is a benefit. It is being researched as a potential therapy for nAMD.
Avacincaptad Pegol is a complement C5 inhibitor.
Complement is thought to be a key factor in AMD-related retinal degeneration. There are currently no FDA-approved stem cell treatments for AMD, however avacinecaptad pegol is being studied as a treatment for GA.
SURGICAL AND OTHER PROCEDURE
The Macular Photocoagulation Study (MPS) has studied laser treatment for CNVMs that are less than 200 microns from the macula's center.
- The first-line therapy for subfoveal CNVMs is anti-VEGF medication.
Although vitrectomy has been done to eliminate CNVMs, it is typically not advised.
CNVMs have the potential to spontaneously bleed, leaving blood under the retina. Within seven days of the bleeding, a vitrectomy should be done to remove subretinal blood, since it may be beneficial. An eye injection of tissue plasminogen activator (tPA) may aid in the removal of a subretinal hemorrhage. In some circumstances, submacular blood may be displaced by intravitreal gas, with or without tPA.
- The treatment of nAMD accompanied by a submacular hemorrhage may benefit from intravitreal anti-VEGF monotherapy.
It is no longer common practice to utilize verteporfin in photodynamic treatment (PDT).
- Patients should be made aware that a 4% chance of severe, sudden vision loss following PDT.
– PDT is less clinically effective than ranibizumab.
– When compared to ranibizumab monotherapy, combination treatment with intravitreal ranibizumab and PDT seems to produce a similar gain in visual acuity.

Alternative Therapies 

Visible light-induced free radical production in the retina may contribute to cellular damage that leads to atrophic/nonexudative macular degeneration. A high-dose regimen of antioxidant vitamins and mineral supplements was found to occasionally slow the progression of AMD by the Age-Related Eye Disease Study (AREDS).
Vitamin C 500 mg, vitamin E 400 IU, -carotene 15 mg, zinc oxide 80 mg, and cupric oxide 2 mg are suggested daily amounts. Smokers should use -carotene with caution because it may increase their risk of developing lung cancer.
The AREDS2 discovered there was no overall benefit to further lowering the risk of developing advanced AMD with the addition of lutein and zeaxanthin, either alone or in combination with omega-3 fatty acids. Vitamin C 500 mg, vitamin E 400 IU, lutein 10 mg, zeaxanthin 2 mg, and zinc 80 mg are the required daily amounts.

Patient Follow-Up Monitoring
Patients with soft drusen or pigmentary alterations in the macula are at a greater risk of vision loss, which can be found using the Amsler grid. They should perform daily Amsler grid tests and follow arbitrary measures of visual acuity, such as reading ability, to keep an eye on their vision. If there are no new symptoms, they should have a follow-up assessment in 6 to 12 months.

Diet

Consuming carotenoids-rich dark green leafy vegetables like spinach and collard greens may lower your chance of getting nAMD.
Omega-3 fatty acid intake and fish eating may lower the risk of AMD.
An Oriental-style diet with higher intakes of vegetables, legumes, fruit, whole grains, tomatoes, and seafood lowers the risk of AMD compared to a Western-style diet with higher intakes of red meat, processed meat, high-fat dairy products, fried foods, refined grains, and eggs. A diet similar to the Mediterranean diet may lower the risk of AMD. A Mediterranean-style diet was linked to a decreased risk of developing late AMD, especially GA, and big drusen.


Patient prognosis: Patients with bilateral soft drusen and pigmentary alterations in the macula but no exudate are more likely to get nAMD and ensuing vision loss.
Patients with nAMD in one eye and drusen in the opposite eye are at an annual risk of 5-14% of getting nAMD in the opposite eye with drusen. Patients with bilateral drusen have a cumulative risk of 14.7% over 5 years of suffering substantial vision loss in one eye from nAMD.
Seven years after receiving ranibizumab therapy, macular atrophy progression and severity were the main morphological drivers of visual outcomes. In eyes receiving anti-VEGF medication, macular atrophy can develop.
Having good eyesight by the fourth VEGF inhibitor injection was closely related to the visual results at three years.
Patients with stable preoperative fluid on OCT and nAMD typically do not experience nAMD worsening following cataract surgery.
Use of aspirin is not significantly linked to development of late AMD. Patients with AMD do not need to avoid taking aspirin when it is prescribed medically.
Nearly 20% of individuals receiving anti-VEGF treatment for nAMD had their useable vision preserved for the course of their average remaining lifetime.


Eyes getting intravitreal anti-VEGF injections should have their intraocular pressure monitored to prevent complications like blindness.
– A higher risk of glaucoma surgery is linked to seven or more IVIs per year as opposed to less frequent administration.

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