Ocular Futility and End of Sight Care

Etiology

Ocular futility can be applied to many aspects of ophthalmologic care.

Ocular Trauma

Severe ocular trauma resulting in an open globe injury can have a guarded prognosis. The ocular trauma score can be utilized to predict outcomes following globe repair.[2] However, regardless of the ocular trauma score, a common practice is to close the globe as soon as possible. Patients with severe globe injuries who undergo primary globe closure are frequently subjected to an enucleation or evisceration procedure within the following days; studies indicate that 10% to 30% of patients have secondary enucleation. The decision to undergo primary enucleation is difficult; many patients with severe ocular injury may be unable to consent, and the psychological burden of removing an eye may be too great in the acute setting.[3][4] In the setting of severe ocular trauma, it can be difficult to determine if it is best to have one less procedure or attempt primary closure.

Advanced Age-related Macular Degeneration (ARMD)

Advanced ARMD is the presence of geographic atrophy or a choroidal neovascular membrane (CNVM). No currently available treatment reverses nonexudative ARMD; geographic atrophy is permanent. However, exudative ARMD is frequently treated with intravitreal anti-vascular endothelial growth factor (VEGF) injections. While the early treatment of CNVM yields excellent visual benefits, as ARMD progresses, the accumulation of atrophy or subfoveal fibrosis inevitably leads to permanent vision loss.[5] The timeline and severity of disease progression are highly variable between patients.

The benefit of continued injections is questionable in patients with neovascular ARMD with a significant atrophic component. One retrospective study suggested that continuing anti-VEGF injections after achieving morphologic and functional stability does not necessarily prevent future exudative changes.[6] This raises the question of when to stop injections, which has no clear answer in the literature. The general practice is to stop anti-VEGF injections when there is a sizeable disciform scar, even if there is a recurrence of fluid or subretinal hemorrhage. However, individual ophthalmologists may differ in their approach.

Strabismus Surgery in a Terminally Ill Child

Strabismus surgery in children is important for reestablishing binocular vision and improving appearance. Although surgery to improve appearance could be categorized as a cosmetic procedure, the importance of appearance on psychosocial development has been highlighted in many studies.[7][8][9] However, determining whether to pursue this type of surgery on a child with a terminal condition is challenging. One case study argues that strabismus surgery is not futile if parents request it, even if the child is terminally ill. The authors of this case study argue that performing the procedure aided the parents in accepting the terminal condition of the child.[10] While this case report raises the important point of family-centered care, deciding to perform such a procedure on a terminally ill child is difficult. 

Advanced Glaucoma

In patients with advanced glaucoma, great efforts are taken to save the last remnants of vision and the visual field. In the most conservative situations, patients with advanced glaucoma are subjected to rigorous drop regimens that place a significant treatment burden on the patient or caregiver and have ocular or systemic adverse effects. These combined barriers frequently lead to therapeutic noncompliance. 

Patients with advanced glaucoma can also be treated with incisional glaucoma surgery. While minimally invasive glaucoma surgery is gaining popularity, traditional tube shunts and trabeculectomy are typical for advanced glaucoma. These surgeries come with a host of potential complications, as the general framework of each procedure is to establish an opening into the eye, which increases the risk of infection, hypotony, and choroidal effusions. In patients with glaucoma refractory to the prior treatments, transscleral cyclophotocoagulation is used, but this procedure comes with its own risk, including a 13% to 50% risk of vision loss.[11][12] 

In a patient with persistently elevated eye pressures with only a central island of vision remaining, providing the most efficacious intraocular pressure (IOP) lowering treatment may seem like the best option. However, the decision is not usually straightforward, and considering potential complications and patient goals is critical. The lack of a thorough understanding of the pathophysiology of glaucoma further complicates these decisions; IOP is currently the only known modifiable risk factor for glaucoma, and every current therapy focuses on IOP reduction. Despite these interventions, many landmark glaucoma trials have demonstrated disease progression in a small percentage of patients despite a good reduction in IOP.[13][14][15]

Advanced Neurotrophic Keratopathy

Neurotrophic keratopathy is most commonly due to a herpetic viral infection. Other causes include topical anesthetic or drop toxicity, burns, chemical injury, contact lens abuse, radiation exposure, and corneal surgery. Neurotrophic keratopathy is challenging to treat; without proper innervation, the cornea loses its ability to maintain its structure and heal wounds. Advanced or stage 3 neurotrophic keratopathy is characterized by corneal ulcers, melting, and perforation. Once the cornea reaches this stage, treatment is limited and corneal transplants do not survive. Without the protective factors provided by innervation, transplanted tissue succumbs to ulceration and melts.[16] 

Advanced neurotrophic keratopathy frequently requires invasive treatments such as conjunctival flaps and temporary or permanent tarsorrhaphies.[17] The decision to perform these procedures is difficult for patients and surgeons alike. These procedures may block the visual axis, preventing the eye from seeing. Although conjunctival flaps and tarsorrhaphies are reversible, deciding if and when to undergo reversal is also challenging, as corneal health may be unchanged. Promising new therapeutic interventions, such as neurotization surgery, are only performed at select tertiary care centers.[18]

Epidemiology

In Denmark, in 2010, the incidence of legal blindness from ARMD was 25.7 per 100,000, an approximate 50% decrease since 2000.[19] 

In the United States, 27% of eyes with severe ocular trauma developed legal blindness.[20] Another study quoted that 35% of eyes with severe ocular trauma developed visual acuity <20/200.[21] 

Primary open-angle glaucoma affects approximately 2% of people over 40 years of age, and the prevalence increases with age.[22] It is difficult for patients with primary open-angle glaucoma to recognize a problem before significant permanent optic nerve damage exists. An Early Manifest Glaucoma Trial screening study identified that 30% of patients with newly diagnosed glaucoma had severe-stage disease in at least one eye.[23]

The incidence of neurotrophic keratopathy is 1 to 5 per 10,000. The results of one study revealed that 30% of eyes with neurotrophic keratopathy required penetrating keratoplasty, 33% of which required multiple transplants within 1 year.[24]

Pathophysiology

Ocular futility describes the state at which further treatment of an ocular disease produces no additional benefit to the patient. Ocular futility is most commonly encountered in ocular diseases with poor visual outcomes. However, ocular futility can also be a consideration for patients with poor life expectancy who may not benefit from an ophthalmic intervention.

History and Physical

In the context of ocular futility, several factors need to be considered in evaluating and managing patients with certain ocular conditions.

Historical factors include a history of congenital or systemic diseases associated with poor life expectancy, ocular trauma, and other debilitating systemic conditions that hinder proper ocular care, such as advanced dementia. Additionally, caregiver or patient fatigue resulting from frequent appointments and a lack of improvement despite therapy should also be considered. Furthermore, poor initial visual acuity and significantly elevated intraocular pressure can serve as important physical examination findings indicating the need for careful consideration of the potential futility of further ocular interventions.

In patients with advanced ARMD, disciform scarring or fibrosis involving the fovea or subfoveal geographic atrophy may indicate continued intervention's futility. In severe ocular trauma, expulsed intraocular contents or a penetrating or perforating injury of the posterior chamber that extends more than 5 mm behind the limbus may indicate further ocular futility. A pale optic nerve head or large cup-disc ratio in advanced glaucoma may preclude the benefit of further treatment. Patients with neurotrophic keratopathy who demonstrate dense band keratopathy, corneal vascularization or edema, subepithelial or stromal infiltrates, or corneal thinning or ulceration may have reached the limits of ocular therapy.

Evaluation

Imaging studies may prove helpful in evaluating the ocular futility of some disease processes.

In patients with advanced ARMD, optical coherence tomography (OCT) of the macula that reveals complete subfoveal effacement of the ellipsoid zone band or significant subfoveal fibrosis in the case of a disciform scar indicates advanced and irreversible damage to the macula, suggesting limited potential for visual improvement with interventions.

OCT of the retinal nerve fiber layer in patients with advanced glaucoma that reveals diffuse thinning of the optic nerve head and visual field testing that demonstrates a significantly decreased mean deviation or a very small island of the visual field indicates severe and irreversible damage to the optic nerve, predicting a poor prognosis for visual recovery despite continued interventions.

In patients with severe ocular trauma, computed tomography of the orbit demonstrating a loss of globe contour indicates severe trauma with possibly irreversible damage, suggesting a limited potential for meaningful visual recovery.

Treatment / Management

A meta-analysis of medical futility suggests that physicians are ultimately in charge of determining when care is futile. The literature has presented various approaches to measuring futility and that joint-decision making with the patient is preferred.[25] Important factors to utilize when making decisions include who will decide on futile care, possible treatment options, the goal of treatment, and the likelihood of achieving said goal.[26] In many conditions, it is very challenging to quantify likelihood as there is a shortage of literature describing end-stage diseases. Regardless, it is the physician's responsibility to help the patient and family understand all these factors about the care the patient is to receive.

Therapeutic intervention can be considered for patients with complete visual loss and persistent eye pain. Retrobulbar alcohol can be utilized to achieve pain control in blind painful eyes. Alcohol destroys the long and short posterior ciliary nerves, preventing pain signal transmission. One retrospective review reported 85% of patients were pain-free after receiving retrobulbar anesthesia, and no patients suffered adverse side effects.[27] Retrobulbar alcohol is a beneficial therapy in a patient with painful blindness who is not psychologically ready for an enucleation or evisceration procedure. Retrobulbar alcohol may also effectively treat phantom pain syndrome after bilateral evisceration.[28]

The Gunderson conjunctival flap surgically transposes conjunctivae to cover the cornea. This procedure can help treat herpetic keratitis, bullous keratopathy, neurotropic keratopathy, and traumatic relapsing keratopathy by decreasing pain from corneal surface injuries and preventing proteolytic enzymes from reaching the cornea.[29] However, amniotic membrane therapy has primarily replaced the conjunctival flap for non–end-stage ocular conditions. Despite newer therapies, the conjunctival flap remains a helpful tool in pain management for patients with severe corneal diseases who are not candidates for keratoplasty. 

Permanent tarsorrhaphy can protect the eye from painful corneal exposure in situations where all other therapies have failed.[30] Evisceration or enucleation can be considered in patients with blind painful eyes, but not all patients have the healthy tenons and conjunctiva required for a successful surgery. A common cause of recurrence of pain after enucleation or evisceration involves dehiscence and exposure of the orbital implant.[31]

Ethical considerations must be made when treating an eye with no light perception. Generally, surgical intervention in an eye with no visual potential is not recommended due to the increased risk of infection and sympathetic ophthalmia to the fellow-seeing eye. Any intervention that could potentially impact the better-seeing eye or the rest of the body must be approached with plenty of caution and restraint.

However, cosmesis could be an indication to pursue surgery if significantly distressing to the patient. For example, leukocoria from a white cataract in an eye with no vision could warrant having a cataract evaluation if the patient has significant psychosocial stress from the appearance of the eye.[32] One study discussed how job applicants with strabismus could be perceived as having less intelligence, aesthetic appeal, and more difficulty finding a job.[33] Thus, the cosmetic appearance of the eye should not be undervalued. There are other less invasive options than full cataract surgery for blind patients with a white cataract, including colored contact lenses, corneal tattooing, and placement of a black sulcus lens.[34][35](B3)

Another situation warranting consideration of incisional surgery is when the pain from the blind eye is caused by an easily modifiable problem such as a retained lens fragment. As always, when making this decision, healthcare practitioners should strive to maintain patient autonomy, beneficence, and nonmaleficence. Pursuing an incisional intervention in a blind eye should only occur after extensive discussion with the patient about their goals, the risks of the procedure, and possible alternative pursuits.

Differential Diagnosis

The following are examples of diseases that may lead to ocular futility:

Advanced ARMD

• Ocular histoplasmosis syndrome
• Myopic degeneration
• Choroidal rupture
• Angioid streaks
• Pattern dystrophy
• Drug toxicity 
• Stargardt and other macular dystrophies
• Central serous chorioretinopathy

Strabismus in a Critically Ill Child

• Decompensated esotropias or exotropias
• Cranial nerve palsies

Advanced Glaucoma

• Toxic or nutritional optic neuropathy
• Arteritic and non-arteritic ischemic optic neuropathies
• Traumatic optic neuropathy
• Compressive optic neuropathy

Neurotrophic Keratopathy

• Dry eye
• Topical drug toxicity
• Exposure keratitis
• Contact lens-related disorders
• Chemical injury
• Limbal stem cell deficiency
• Acanthamoeba keratitis
• Herpetic keratitis

Prognosis

Ocular futility can only be considered in patients with a terminal prognosis from either an ocular condition or a systemic disease that precludes further ocular therapy.

Complications

Treating patients that could be deemed ocularly futile puts them at risk of complications from an intervention.

Repeat intravitreal anti-VEGF injections for patients with advanced ARMD can lead to endophthalmitis, although the occurrence is rare and has been reported as 1 case per 2578 injections.[36] Eviscerations and enucleations also have many risks; a retrospective case series reported a reoperation risk of 14%.[37] Treating a patient with end-stage glaucoma with a trabeculectomy or drainage implant increases their risk of infection to approximately 3%.[38] Other vision-threatening complications of these procedures include cataracts, hypotony, wound dehiscence, choroidal effusions, and procedure failure.[39]