Didanosine Retinal Toxicity

Haug, Sara J.; Wong, Robert W.; Day, Shelley; Choudhry, Netan; Sneed, Scott R.; Prasad, Pradeep; Read, Sarah P.; McDonald, R. H.; Davis, Janet L.; Sarraf, David

doi:10.1097/iae.0000000000001267

Cited by 26 publications

(44 citation statements)

References 15 publications

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“…HAART utilises dual class, triple combinational therapy, usually 2 nucleoside/non-nucleoside reverse transcriptase inhibitors and 1 protease inhibitor (e.g. ritonavir) [7,13]. DDI-associated retinal toxicity (DART) with peripheral chorioretinal atrophy was reported as early as 1992 in a phase 2 study in 5 out of 95 children [16], and similar findings were reported amongst HIV-positive adults in 1996 [4].…”

Section: Discussionmentioning

confidence: 93%

“…To date since 1992, there have been numerous reported cases of didanosine-associated retinal toxicity (DART) amongst adults [4][5][6][7][8][9][10][11]. The reported clinical findings of DART range from mild mid-peripheral pigmentary stippling to extensive patches of chorioretinal atrophy which can affect the macula in advanced cases [4][5][6][7][8][9][10][11]. Patients are initially asymptomatic, but in advanced disease, they can present with significant peripheral visual field defects and nyctalopia [4][5][6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

“…The reported clinical findings of DART range from mild mid-peripheral pigmentary stippling to extensive patches of chorioretinal atrophy which can affect the macula in advanced cases [4][5][6][7][8][9][10][11]. Patients are initially asymptomatic, but in advanced disease, they can present with significant peripheral visual field defects and nyctalopia [4][5][6][7][8][9][10][11]. Despite the cessation of DDI, in some cases, the chorioretinal atrophy continues to extend posteriorly with resultant severe visual field constriction [7].…”

Section: Introductionmentioning

confidence: 99%

“…Patients are initially asymptomatic, but in advanced disease, they can present with significant peripheral visual field defects and nyctalopia [4][5][6][7][8][9][10][11]. Despite the cessation of DDI, in some cases, the chorioretinal atrophy continues to extend posteriorly with resultant severe visual field constriction [7]. In vitro studies show that DDI and other NRTIs bind to and inhibit the action of mitochondrial γ DNA polymerase disrupting mitochondrial replication and hence energy production [12,13].…”

Section: Introductionmentioning

confidence: 99%

“…In vitro studies show that DDI and other NRTIs bind to and inhibit the action of mitochondrial γ DNA polymerase disrupting mitochondrial replication and hence energy production [12,13]. It is thought that retinal toxicity associated with DDI use is due to its mitochondrial toxicity [7,12,13], and other ocular manifestations of mitochondrial toxicity such as ptosis, ophthalmoplegia [14] and optic neuritis [15] have been reported. Herein, we describe four cases of DART in HIV-positive adult patients.…”

Section: Introductionmentioning

confidence: 99%

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Didanosine-Associated Retinal Toxicity (DART) Amongst HIV-Positive Patients: a Case Series and Literature Review

Nderitu

Riga

Mann

et al. 2020

SN Compr. Clin. Med.

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The aim of this study is to report on didanosine-associated retinal toxicity (DART) in four adult patients with human immunodeficiency virus (HIV) identified incidentally during routine diabetic eye screening and review all reported cases to date. This study is a retrospective, observational, case series from two health institutions with a review of published literature. DART is often asymptomatic, and patients have good vision (mean visual acuity 6/9), but in advanced cases, severe visual field defects can occur. Fundal changes range from mild granular pigmentary mottling to patches of mid-peripheral chorioretinal atrophy. Continuous expansion of chorioretinal degenerative changes posteriorly may lead to significant macular involvement as demonstrated in two of our cases. Despite cessation of therapy, DART was progressive in approximately 25% of reported cases. Our cases were incidentally discovered during routine diabetic eye screening and did not report any ocular symptoms prior to referral. Given the initial asymptomatic nature of DART, we believe that the true prevalence of the disease may be higher than previously thought. It may be prudent to screen and follow-up patients with a history of DDI use. We demonstrate the utility of multimodal imaging, optical coherence tomography, electrodiagnostic testing and visual fields in evaluating the effects of DART.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Didanosine-Associated Retinal Toxicity (DART) Amongst HIV-Positive Patients: a Case Series and Literature Review

Nderitu

Riga

Mann

et al. 2020

SN Compr. Clin. Med.

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CHM mutation spectrum and disease: An update at the time of human therapeutic trials

et al. 2021

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Choroideremia is an X‐linked inherited retinal disorder (IRD) characterized by the degeneration of retinal pigment epithelium, photoreceptors, choriocapillaris and choroid affecting males with variable phenotypes in female carriers. Unlike other IRD, characterized by a large clinical and genetic heterogeneity, choroideremia shows a specific phenotype with causative mutations in only one gene, CHM. Ongoing gene replacement trials raise further interests in this disorder. We describe here the clinical and genetic data from a French cohort of 45 families, 25 of which carry novel variants, in the context of 822 previously reported choroideremia families. Most of the variants represent loss‐of‐function mutations with eleven families having large (i.e. ≥6 kb) genomic deletions, 18 small insertions, deletions or insertion deletions, six showing nonsense variants, eight splice site variants and two missense variants likely to affect splicing. Similarly, 822 previously published families carry mostly loss‐of‐function variants. Recurrent variants are observed worldwide, some of which linked to a common ancestor, others arisen independently in specific CHM regions prone to mutations. Since all exons of CHM may harbor variants, Sanger sequencing combined with quantitative polymerase chain reaction or multiplex ligation‐dependent probe amplification experiments are efficient to achieve the molecular diagnosis in patients with typical choroideremia features.

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Drug-Induced Neuro-ophthalmological Disorders

Jain

2021

Drug-Induced Neurological Disorders

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Didanosine Retinal Toxicity

Cited by 26 publications

References 15 publications

Didanosine-Associated Retinal Toxicity (DART) Amongst HIV-Positive Patients: a Case Series and Literature Review

Didanosine-Associated Retinal Toxicity (DART) Amongst HIV-Positive Patients: a Case Series and Literature Review

CHM mutation spectrum and disease: An update at the time of human therapeutic trials

Drug-Induced Neuro-ophthalmological Disorders

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