Article

A Case of Particulate Retinopathy

Diamonds are forever.

There are many different etiologies of acquired particulate retinopathy, some of which are potentially blinding differential diagnoses. Small refractile crystalline deposits arrive into the retinal vasculature through processes that can cause a wide variety of prognoses from progressive and ischemic to asymptomatic and static retinopathies.1-2 Particulate matter from chronic drug use or environmental exposure can be inhaled, swallowed, or injected intravenously, eventually causing certain microparticles to compromise cardiopulmonary capillary beds.1-3 Over time, these particles can become lodged in the retinal vasculature as collateral vessels form in response to ischemia.1-3 It is important to identify ocular manifestations of such particulate retinopathies to help treat or identify the underlying cause, preventing further retinal damage and loss of visual acuity.

Case Report

A 48-year-old black male presented to clinic for a dilated eye exam. The patient had no chief complaint and was oriented to time and person. The patient was treated for hyperlipidemia and was a current 20-pack-year smoker. The patient denied recreational drug or alcohol use. He denied ocular trauma or surgery and his family history was unremarkable for any ocular pathology. He had no known drug allergies.

His entrance exam testing showed best corrected acuity at 20/20 OD and OS without correction, EOM testing were full without restriction, and no APD was noted OU. Intraocular pressures were normotensive and slit lamp biomicroscopy was unremarkable for pathology OU. The patient was dilated using one drop 0.5% proparacaine, one drop 1% propicamide and one drop 2.5% phenylephrine OU.

Dilated fundus examination showed multiple bright glistening refractile crystals scattered throughout the posterior pole OS>OD. No RNFL dropout was noticed OU and there was a pigmented vitreoretinal tuft seen at 1030 OD without evidence of retinal break or detachment OU.

The optic nerve showed a cup to disc ratio of 0.55/0.6 OD and 0.6/0.65 OS without evidence of notching or disc hemorrhage. There was no sign of anterior or posterior segment neovascularization or acute retinopathy. The fundus and periphery was otherwise unremarkable.

Fundus imaging (Figures 1 and 2) demonstrated multiple scattered bright refractile bodies OS>OD, which became more prominent with red free photography. No atrophic changes were noted on fundus autofluorescence imaging. There was no evidence of RNFL dropout noted with fundus photos or dilated fundus examination OU. The findings are shown below.

Figure 1. Montage of fundus photography showing color, red-free, and FAF imaging OD. Red arrows show scattered bright refractile bodies, most marked with red-free imaging.

Figure 2. Montage fundus photography showing color, red-free, and FAF imaging OS. Red arrows show scattered bright refractile bodies, most pronounced with red free imaging, slightly more apparent than OD.

Cirrus optical coherence tomography (OCT; Carl Zeiss Meditec) of the macula was performed and demonstrated several small hyper-reflective particulates scattered throughout the inner retina (Figures 3 and 4). Otherwise, the retina appeared healthy and all layers were intact. Ganglion cell count analysis was unremarkable as well (Figure 5) and showed no signs of RNFL loss.

Figure 3. OCT of the right eye showing hyper-reflective bodies within the inner retina (red arrows).

Figure 4. OCT of the left eye showing hyper-reflective bodies within the inner retina (red arrows).

Figure 5. Refractile bodies are visible in the nerve fiber layer, the ganglion cell layer, along with the inner nuclear and inner plexiform layers. This is also evident in the OCT images in Figures 3 and 4.

The patient was worked up for retinal emboli, including a carotid Doppler ultrasound, complete blood count with differential, metabolic and lipid panels, CRP, and ESR. The retina specialist on call was consulted and agreed to see the patient after the initial screening tests were completed.

Differential Diagnosis

Particulate retinopathy is, in essence, a diagnosis of exclusion. The first cases of particulate retinopathy were in the form of “talc retinopathy” dating back to the turn of the 20th century, manifesting as bilateral small refractile bodies dispersed throughout the posterior pole. Different clinical etiologies can manifest crystalline or particulate retinopathy. Systemic conditions as well as those with a history of chronic drug use or prolonged exposure to toxins can contribute to and exacerbate this condition. The differential diagnosis can be broken down as follows.

Manifestations From Systemic Etiologies

Oxalosis is a pathologic deposition of an insoluble salt, calcium oxalate, in various tissues throughout the body.4,5 This metabolic disorder causes a deficiency in the enzymes needed to break down calcium oxalate.4,5 Over time, these salts can accumulate and cause retinopathy, specifically at the level of the retinal pigment epithelium (RPE), causing a hypopigmented ring around a hyperpigmented central area.4 This can lead to the formation of a macular plaque, causing vision loss.4 This condition can resemble fundus albipunctatus and stems from long-term use of anesthesia.4

Cystinosis is a rare lysosomal disorder resulting in intracellular accumulation of cysteine crystals in varying tissues throughout the body.4 Kidney dysfunction is almost always present in those presenting with ocular findings.4 Crystalline deposits can be present in the cornea, conjunctiva, and retina.4-5 Cystinosis can also cause degeneration and atrophy of the RPE.4

Sjogren-Larsson syndrome is a metabolic abnormality presenting with a deficiency in the enzyme fatty aldehyde dehydrogenase.4 This leads to the inability to break down long- and medium-chain fatty aldehydes into corresponding fatty acids.4 These patients present with bilateral crystals in the foveal and parafoveal regions, which can vary in size and are specifically located in the inner-most retinal layers.4

Retinal emboli include calcific emboli, cholesterol emboli, and fibrinoplatelet emboli. Calcific emboli are bright, larger in size, and tend to be closer to the optic nerve. These types of emboli usually present in older patients with calcific aortic stenosis.7-8 Cholesterol emboli (Hollenhorst plaques) are present in patients with atherosclerotic disease, appearing bright and shiny, lodged within a vessel.6-8 Ulcerative plaques and hemodynamically significant stenosis is typically seen with carotid artery disease.6-8 Fibrinoplatelet emboli are faded, nonrefractile, elongated plaques arising from ulcerative plaques from the ipsilateral internal carotid artery or from abnormal heart valves.7-8

Drug-Induced Particulate Retinopathies

Tamoxifen is a nonsteroidal antiestrogen medication used in the treatment of breast cancer.4-5 The toxicity is seen most notably as cornea verticillata (which resolves with lower doses of tamoxifen), but fine white, refractile bodies can be seen in the nerve fiber and inner plexiform layers of the retina.4-5 These bodies are usually present in the posterior pole, but have been found as far out as the ora serrata, which does not resolve after lessening or cessation of the medication.4

Talc is a mineral used in baby powder that is also crushed up and used as a “filler” to add weight to recreational drugs.1,3-6,9 Retinopathy can be seen in chronic users, but the size of such particulates has to be smaller than the diameter of the retinal vasculature (3.5 µm to 5 µm) to occlude such vessels.1,3-6,9 In the acute stages of talc retinopathy, cotton wool spots and retinal hemorrhages can be seen, although in chronic cases, small glistening particulates can be seen in high concentrations around the macular area.3-6,9 Specifically, the nerve fiber layer and inner nuclear layers of the retina are affected.3-6 These patients may also have pulmonary and cardiovascular issues from prolonged damage from ingesting these fine starch spherules.3-6,9

Canthaxanthine is a naturally occurring carotenoid.4,5 Approved by the FDA as a red food coloring and used to treat photosensitivity, it was introduced in 1979 as an over-the-counter oral tanning agent.4,5 Retinopathy is seen in higher quantities of canthaxanthine ingested and presents with golden crystalline deposits in the nerve fiber layer surrounding the fovea.4,5 These deposits remain static even after discontinuation of the medication.4

Other Ocular Differentials

Gunn dots are prominent footplates of Mueller cells, typically seen as large white bodies overlying large vasculature in areas of abundant nerve fiber layer.3,4,6 They can appear variable in intensity and have no pathologic consequence. They are visible reflections of the internal limiting membrane, most prominent around the optic nerve head.3,4,6

Macular drusen are small yellowish round particles, made up of lipids, that can appear anywhere along the fundus.4,6 They are located mostly under or, at times, immediately above the RPE.4,6 The presence of drusen can be seen well with OCT imaging in conjunction with a dilated fundus examination.3,4,6

Diagnosis

The results of our patient’s workup illustrated an elevated low density lipoprotein level (around 148 mg/dL); otherwise, his labs were unremarkable. Carotid duplex revealed no hemodynamically significant stenosis and no evidence of ulcerative plaque formation on either side of the carotid artery, nor did he have an audible bruit. The patient did not present with any other anterior- or posterior-segment finding other than scattered bright particulates in the superficial retina throughout the posterior pole. He denied any prior surgeries and use of recreational drugs and medications that have associations with particulate retinopathy. He was oriented to time and person and had no congenital birth defects nor change in mental status.

Hollenhorst plaques were at the top of our differential diagnosis, but considering the patient’s young age, scattered inner retinal crystalline particles with OCT imaging and a clear carotid ultrasound, particulate retinopathy seemed more likely. The patient presented with an intact, impervious RPE with refractile particulates located in the more inner retina layers. Due to the patient’s history of working as a jeweler and cutting precious stones for 18 years without a recommended respirator, the findings were most consistent with diamond dust embolization to the retina.

A carefully placed OCT scan showed these tiny refractile particles were localized to the inner retina in both eyes. These particulates were scattered throughout, but not limited to, the posterior pole. The patient was told to wear a mask and eye protection at work, and was diagnosed with a static “diamond dust” retinopathy and to return to optometry for his yearly comprehensive exams.

Discussion

The pathogenesis and diagnosis of particulate retinopathy is dependent on prior exposure to toxins or environmental factors, as well as the overall systemic history of the patient. Considering that optometrists may be the first to identify such particulates, it is important to find not only the underlying cause, but any resulting complications that may arise in vivo.

While several exogenous substances can embolize to the retina, one of the most common forms of particulate retinopathy is talc, which presents as minute crystalline deposits within the microvasculature of the retina.1-6,9-11 Due to its prevalence, “microtalc particulate retinopathy” or “talc retinopathy” has culminated the most research in the eye care field.1-6 As a result, there are limited data suggesting that other forms of particulate retinopathies have manifested to the eye, although the pathophysiology proves it is possible.1-6,9-11

Talc, a substance used as a filler in many street drugs such as “free basing” crack cocaine have been found to embolize to the eye.1-6,9,10,12 Once these micro-occlusive particles enter systemic circulation, endothelial cell proliferation and the initiation of chemo-attractant and immune modulatory pathways can cause a compromise to lumen integrity.1-6,9-12 The result is pulmonary hypertension and subsequent shunting of blood through newly developed collateral vessels in response to ischemia from multiple microemboli within the cardiopulmonary capillary bed.1,3,6,9,12 These new vessels allow shunting of venous blood around compromised vasculature, allowing larger particles in the blood to entering systemic circulation.1,3,6,9,12 Normally, exogenous particles greater than 7 µm cannot pass through healthy pulmonary circulation; however, once collateralization has occurred, larger particles upwards of 10 µm to 15 µm can enter systemic circulation.1,3-6

The microvasculature of the eye is most affected at areas of heightened vascular supply in the retina, mainly at the posterior pole.1,3,4,6,14 Blood is supplied to the eye from the ophthalmic artery, a branch of the internal carotid artery.14 The central retinal artery, a branch off the ophthalmic artery, supplies the inner retina.14 The external retina, photoreceptors, and RPE are supplied by the posterior ciliary arteries.14 Once particles embolize to the retina, the highest concentration can be seen at the inner nuclear, outer plexiform, and deep choroidal plexus.1,6,14 Due to chronic exposure and the proven formation of cardiopulmonary collateral vessels, it becomes apparent that any form of exogenous microdebris can embolize to the retinal vasculature. These emboli may cause occlusive events, leading to retinal ischemia and capillary nonperfusion, leading to neovascularization and other potentially blinding sequelae.1-6,10-12

Martidis et al described a case of retinal embolization from talc particles in a middle aged man which remained lodged in the retinal vessels over a 2-year period with no hypoxia, neovascularization, or change in funduscopic presentation.9 The frequency of complications is unknown; however, literature suggests that most cases of particulate retinopathy have a predilection for causing a static retinopathy.9 Over time with prolonged exposure, however, fully occluded arterioles can lead to ischemia and can result in neovascularization and other resulting complications within the affected retina, including vitreous hemorrhages, tractional retinal detachments, and axoplasmic stasis.1-6,9,10,12 Patients with suspected neovascularization must be sent for panretinal photocoagulation and fluorescein angiography to properly evaluate all areas of ischemia and leakage.1,3-6,9-12 Proper blood panels should be obtained to determine other risk factors for vasculopathic causes for development of neovascularization.

Besides those with chronic exposure to systemic microinhaled or injected particles, those born with a patent foramen ovale are more likely to develop such paradoxical embolic events.1,3-5,13 A patent foramen ovale is a congenital birth defect where the opening between the 2 upper atrial septa (primum and secundum) does not close after birth.13 Occurring in about 27% of the population, this mechanism mimics the pathogenesis of talc retinopathy, in which the heart bypasses pulmonary circulation allowing large particles to travel freely in systemic circulation, embolizing in microvasculature in areas distal to the heart.1,3-5,13

Fluorescein angiography of patients with particulate retinopathy will reveal capillary nonperfusion, or resulting leakage and ischemia if extensive arterioles throughout the retina are occluded.1,3,4,6,9 Schatz and Drake found capillary nonperfusion on fluorescein angiography in 3 of 12 eyes with talc retinopathy, leading to speculation of entrapment of ischemia from multiple small emboli within a capillary bed.15 In our patient’s case, his lungs were already compromised by more than 20 pack years of smoking and repeated exposure to diamond and jewel dust. OCT imaging revealed emboli along the inner retina (see Figures 4 and 5) and a diffuse presentation of bright particles bilaterally throughout the posterior pole. These findings remained unchanged in subsequent visits to the clinic and, after ruling out a high-risk vasculopathic profile or carotid occlusive disease, the anatomy and ocular presentation was most consistent with static “diamond dust” retinopathy.

Conclusion

In this case, a proper workup with fundus photography, OCT imaging, carotid Doppler, lab work, and a full dilated examination were required to rule out other potentially blinding ocular etiologies. The patient presented with and remains to have a rare case of static particulate retinopathy in the form of diamond dust after years of exposure without proper protection. All forms of embolic and occlusive vasculopathies and retinopathies were considered before making this diagnosis of exclusion. It is the role of the eye care provider to properly follow and manage these cases to rule out any form of ischemic or progressive retinopathy in the case that the underlying cause is not properly managed. Furthermore, a proper history is imperative for a comprehensive eye examination, even in the setting of healthy patient’s without a presenting ocular complaint.

References

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