Surgical management of a case of severe leukemic retinopathy

Abstract

Purpose

To present a case of severe leukemic retinopathy requiring surgical rehabilitation. We report four-year follow up and associated post-remission pathology including cystoid macular edema (CME) and retinal ischemia.

Observations

This is a case report of a 35-year-old female with acute myelocytic leukemia (AML) who presented with hand motions (HM) vision in both eyes and severe multilayered hemorrhages. She underwent pars plana vitrectomy (PPV) in the left eye and subsequent PPV with internal limiting membrane (ILM) peel in the right eye after autologous bone marrow transplant. After cataract surgery and treatment of CME, visual acuity improved to 20/25 in each eye. Fundus examination and optical coherence tomography (OCT) revealed outer retinal loss outside of the fovea.

Conclusions and importance

Surgical intervention can be necessary for visual rehabilitation in some patients with leukemic retinopathy. With improved medical treatment for AML, patients survive longer, making visual rehabilitation more impactful and allowing for a better understanding of the natural history of leukemic retinopathy.

1. Introduction

Leukemias are myeloproliferative disorders with ocular involvement in over 80 % of cases.¹ They are grouped into acute or chronic with acute leukemias presenting with a more aggressive course and a higher proportion of immature blast cells. They are also differentiated based on the cellular lineage, with myeloid leukemia deriving form myeloid progenitor cells.1, 2, 3 Ocular involvement is more commonly seen in acute leukemias and can include infiltration of the orbit, optic nerve, choroid, retina, iris, ciliary body, and the anterior chamber.^1,2 Hemorrhages of various structures including the retina, vitreous, anterior chamber and subconjunctival space have also been reported.^2,3

Ocular findings can occur either due to direct invasion of leukemic cells or secondary to associated anemia, thrombocytopenia, or hyper-viscosity. Advancements in treatment have improved survival in acute myeloid leukemia (AML), yet prognosis can vary with an overall 3-year survival ranging from 4 % to 75 % depending on age and risk stratification.⁴ With improved survival, visual rehabilitation becomes of greater significance. In many cases, intraocular disease is managed by observation while the patient undergoes systemic treatment. However surgical intervention such as pars plana vitrectomy for retinal detachment repair, non-clearing vitreous hemorrhage, and diagnostic biopsies have been reported.5, 6, 7, 8, 9, 10, 11 Here we describe a case of severe bilateral leukemic retinopathy managed with successful surgical intervention and also describe the four-year follow up and disease course.

2. Case report

This work was reviewed by the institutional review board at the University of Iowa and was deemed non-human-subjects research. A previously healthy 35-year-old female presented to an outside hospital with 2–3 months of progressive fatigue, easy bruising, and unintentional weight loss attributed to a sinus infection. Bloodwork revealed severe anemia (hemoglobin 4.6 g/dL), thrombocytopenia (platelets 8000/mm³), and leukocytosis (37500/mm³) with a peripheral smear showing circulating blasts of myeloid origin. She was diagnosed with AML and received blood and platelet transfusions.

She reported blurred vision in both eyes and was evaluated by ophthalmology. She was found to have 20/400 vision in the right eye and count fingers vision in the left eye with multiple sub-hyaloid, intra-retinal, subretinal/sub-internal limiting membrane (ILM), and suprachoroidal hemorrhages worse in the left eye (Fig. 1a–b). She developed acute worsening of her vision and was found to have developed bilateral break-through vitreous hemorrhages with a decline in vision to hand motion in each eye (Fig. 1c–d). Given the limited funduscopic view, magnetic resonance imaging (MRI) of the orbits was also obtained and showed no leukemic infiltrate of the optic nerves.

Fig. 1.

Color fundus photographs and B-scan echography at presentation. A and B show color fundus photographs of the right (A) and left (B) eye respectively with severe sub-hyaloid/sub-ILM (white arrows), intra-retinal (red arrows), subretinal (blue arrows), and suprachoroidal hemorrhages (yellow arrows) in both eyes. Visual acuity was 20/500 in the right eye and count fingers in the left eye at initial presentation. C and D show B-scan echography of the right (C) and left (D) eyes after development of break-through vitreous hemorrhage (Echo image cuts T9P = transverse 9:00 posterior). Used with permission from Springer Publishers and The University of Iowa EyeRounds.org19, 20 (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

She was started on daunorubicin and cytarabine with a plan for subsequent autologous bone marrow transplant. In the meantime, her vision did not improve and the vitreous hemorrhages continued to worsen. After an extensive discussion with the patient and her medical oncology team, the decision was made to proceed with limited pars plana vitrectomy in the left eye to clear the visual axis prior to autologous bone marrow transplant in an effort to restore ambulatory vision. During surgery, after the core vitrectomy was performed, the posterior pole was visualized and a massive sub-ILM hemorrhage involving the entire posterior pole and nasal midperiphery, with a possible subretinal component, was noted. There was a choroidal hemorrhage in the inferotemporal periphery. The posterior hyaloid was attached and it was felt to be unsafe to lift the taut posterior hyaloid in the setting of her peripheral ischemic retina and risk for creating a retinal break. Therefore, no posterior vitreous detachment was induced and the eye was left under fluid.

The vision in the left eye improved to 20/300 by post-operative month one. Following bone marrow transplant and stabilization of her blood counts, there was further clearing of the sub-hyaloid hemorrhage and visual acuity improved to 20/100 in each eye by post-operative month four. Once the view improved to be able to obtain OCT, there was cystoid macular edema (CME) noted. The CME was presumed to have a contributions from retinal microvascular disease in the setting of her underlying blood dyscrasia with a possible superimposed component of post operative CME. Fluorescein angiogram was deferred given the limited view from residual vitreous hemorrhage and the necessity to avoid exposures in the eye clinic given her immune suppression and the COVID-19 pandemic. She was offered a trial of both topical and intra-vitreal steroids and was started on topical difluprednate 0.05 % (Durezol®) drops three time daily in the left eye for treatment of the CME. Durezol was selected as a more potent topical steroid with fewer daily doses given her limited ability to instill drops in the setting of her poor vision.

By post-operative month five, she had achieved remission. The visual acuity remained 20/500 in the right eye with persistent vitreous hemorrhage and was 20/100 in the left eye. The decision was made to proceed with PPV with ILM peel for residual dense sub-hyaloid and sub-ILM hemorrhages in the right eye (Video). A standard three port vitrectomy was performed with removal of the central vitreous and dense dehemoglobinized vitreous hemorrhage. A partial posterior vitreous detachment was noted to be present. To avoid peripheral traction on the ischemic retina, vitreous was circumscribed from the posterior pole and then shaved from the vitreous base. A bent microvitrectomy blade was used to create an opening in the ILM in the temporal macula. The ILM was grasped with ILM forceps and was gently elevated from the surface of the sub-ILM hemorrhage. Tissue blue dye was instilled in order to better visualize the remaining ILM which was gently peeled from the central macula. A combination of ILM forceps and the vitreous cutter were used to remove the dense sub-ILM hemorrhage from the macula. The peripheral retina was carefully inspected and there were no peripheral retinal breaks, although the retina appeared ischemic. Twenty-two percent SF6 gas was placed due to concern for a small retinal break in the inferior macula. Two weeks after vitrectomy in the right eye, the visual acuity had improved to 20/70 in the right eye and remained 20/100 in the left eye.

Post operatively, CME was present in both eyes and outer retinal atrophy with ellipsoid zone (EZ) loss outside of the fovea was noted on OCT (Fig. 2). She underwent intravitreal triamcinolone acetonide injection in the right eye with good response after one injection but with recurrence one month later. For the left eye, the difluprednate drops were ineffective, and she was treated with intravitreal triamcinolone acetonide injection with good response but recurrence after one month. The CME subsequently resolved with one dexamethasone intravitreal implant injection in the right eye and three injections in the left eye (3–5 months apart). She subsequently developed cataracts in both eyes and underwent uncomplicated cataract extraction outside of our institution. There was no recurrent CME following cataract extraction. Four years after initial presentation, her acuity is 20/25 in each eye with resolved CME (Fig. 3). She remains in remission.

Fig. 2.

Color fundus photographs and OCT 2 weeks following vitrectomy with ILM peel in the right eye (five months following limited vitrectomy in the left eye). A and B show mild residual dehemoglobinized vitreous and pre-retinal hemorrhage with ischemic/pigmentary changes in the periphery (note mild residual SF6 gas superiorly in the right eye). C and D show corresponding OCT images of the maculae of both eyes with marked cystoid macular edema and parafoveal outer retinal atrophy. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 3.

Color fundus photographs and OCT four years after presentation. A and B show optos pseudo-color photographs of both eyes with stable pigmentary changes in the periphery. OCT of the right and left eyes (C and D) show resolution of the previous cystoid macular edema and parafoveal outer retinal and ellipsoid zone loss. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

3. Discussion

Leukemic retinopathy can present with a broad spectrum of disease severity that ranges from visually insignificant intra-retinal hemorrhages to severe optic nerve infiltration with risk for permanent vision loss.¹² There are currently no uniform screening guidelines for ophthalmic exams for patients with newly diagnosed acute leukemia. However, given the potential for permanent vision loss from processes such as optic nerve infiltration and retinal vein occlusion from stasis retinopathy, patients with newly diagnosed leukemia should be examined urgently with any report of vision loss.¹² As illustrated by this case, bilateral severe sub-ILM and sub-hyaloid bleeds can cause rapid vision loss and functional decline for patients creating an additional challenge as they face the need for aggressive systemic therapy.

While many cases of leukemic retinopathy can be managed medically, this case highlights the role for surgical intervention in severe cases. The decision to proceed with surgery must be carefully coordinated with the patient's medical oncology team given the immune compromise and blood dyscrasia caused by both the underlying leukemia and its treatment. Further, the surgical approach must be carefully planned as challenges such as the attached posterior hyaloid in young patients, positioning limitations when patients require other procedures, and retinal ischemic changes can influence the timing and surgical approach. As demonstrated by this case, one may choose to perform less aggressive vitrectomy surgery as we did for this patient's left eye to minimize risk and restore visual function as patients progress through treatment while saving more aggressive maneuvers until patients are systemically stabilized.

Our surgical approach for the right eye highlights techniques such as carefully circumscribing the posterior vitreous rather than aggressively lifting the posterior hyaloid in order to minimize the risk for creating retinal breaks in eyes with peripheral ischemic changes (Video). Peeling the hyaloid and ILM may aid in clearing sub-hyaloid and sub-ILM hemorrhages but also carries the risk for retinal breaks and further hemorrhage which we tried to minimize by carefully using forceps to remove the ILM along with the use of tissue blue dye to visualize tissue planes. While we were able to achieve a much quicker visual recovery for our patient's right eye using this approach, it is important to note that the final outcomes of both eyes was similar as the sub-hyaloid and sub-ILM hemorrhages in the left eye did eventually clear on their own. This is similar to work by Ghoraba et al. that showed a 20/20 visual outcome in both eyes of a young patient with bilateral macular sub-ILM hemorrhages due to Terson syndrome where one eye was managed with vitrectomy and the other eye was observed as the hemorrhage slowly cleared.¹³ Our case highlights the need to make surgical decisions on a case-by-case basis with the status of the fellow eye and the patients systemic disease control playing a role in surgical timing and degree of intervention.

The extensive retinal ischemia, development of CME, as well as loss of outer layers and the EZ band, with foveal sparing on OCT is of note in this case. It is uncertain whether pre-retinal hemorrhages could have caused toxicity to the photoreceptors. This seems unlikely, as there were significant pre-macular hemorrhages yet the macula and fovea had outer layer sparing relative to more peripheral retina. Areas of resolved intra-retinal or subretinal hemorrhage may have contributed to the outer retinal attenuation seen in this case. Recent OCT angiography studies have pointed to retinal microvascular ischemia in acute leukemic patients even prior to presentation with leukemic retinopathy.^14,15 Interestingly, Lee et al., did not find changes in choriocapillaris vascular density in leukemic patients.¹⁴ However, our patient had primarily photoreceptor and EZ loss. This could be secondary to a paraneoplastic effect akin to cancer associated retinopathy or secondary to choroidal blood flow compromise that was not able to be measured via choriocapillaris density measurement in previous studies. Interestingly, others have reported outer retinopathy in the spectrum of acute macular neuroretinopathy (AMN) in leukemias16, 17, 18 and have suggested a possible immune-mediated microangiopathy as the underlying mechanism.¹⁶ The OCT in our case is more compatible with diffuse rod loss rather than an AMN like presentation yet it may also have an immune-mediated etiology. Examining patients with acute leukemia with newer imaging modalities such as OCT-A may provide more insight into the mechanisms behind photoreceptor loss and development of CME.

4. Conclusion

This case demonstrates a severe presentation of leukemic retinopathy and highlights the role of surgery in select cases. The decision to proceed with surgery must be carefully timed and balanced with the associated risks, but can be of benefit in severe cases such as this. The OCT findings in this patient are also of note. More work needs to be conducted regarding the etiology of the diffuse outer retinal loss with foveal/macular sparing in patients with leukemic retinopathy.

CRediT authorship contribution statement

Farzad Jamshidi: Writing – review & editing, Writing – original draft, Data curation, Conceptualization. Timothy M. Boyce: Writing – review & editing, Data curation, Conceptualization. R. Christopher Bowen: Writing – review & editing, Data curation, Conceptualization. H. Culver Boldt: Writing – review & editing, Conceptualization. Elaine M. Binkley: Writing – review & editing, Writing – original draft, Supervision, Formal analysis, Data curation, Conceptualization.

Patient consent

The patient gave written consent to publish this case.

Acknowledgements and disclosures

None.

Funding

No funding or grant support

Declaration of competing interest

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: No relevant financial disclosures for any author.

Appendix A. Supplementary data

The following is the Supplementary data to this article.