Colorado drugged driving prevalence and impaired driving conviction rates: Effects of impaired driving definitions and a 5-nanogram limit for delta-9 tetrahydrocannabinol.

Objectives: How prevalent is drugged driving among Colorado drivers convicted of Driving Under the Influence (DUI)? What are the conviction rates of Colorado drivers charged with DUI, including impairment by marijuana's delta-9 tetrahydrocannabinol (THC)? Is Colorado's THC permissible inference law effective? To answer these questions, this report analyzes data published primarily in appendices of Colorado drugged driving reports.Methods: In 2017 Colorado began requiring annual analyses of Driving Under the Influence (DUI) offenses, including causes and judicial consequences of DUI offenses. These analyses are performed by the Division of Criminal Justice's Office of Research and Statistics (ORS) within the Department of Public Safety. Each analysis requires ORS to link toxicology and court data bases. Data linking enables reporting of charges and convictions by categories including alcohol only, THC only, and polydrug use (two or more drugs simultaneously). Reports have been published annually for 5 years, the latest published in 2023 which covers case filings for 2020.Results: A rough estimate of one-half of the state's DUI filings were attributed to drug use and half were attributed to alcohol only. The largest component of drugged driving was polydrug impairment, rather than impairment by a single drug like THC. Conviction rates in 2020 were 91% for alcohol only, 90% for polydrug cases, and 72% for THC only. Blood drug levels and law structure (per se, permissible inference, DUI definition) affected conviction rates significantly by defendant subsets. THC conviction rates in 2020 ranged from 11% to 100%, depending on blood drug levels and the legal charges.Conclusions: Efforts to educate the public about the dangers of drugged driving should emphasize polydrug impairment, not simply THC impairment. States should analyze data on causes and consequences of DUI arrests to understand what their drugged driving problems are and what they are not. Non-zero drug per se levels and defining DUI as "incapable of safe driving" can severely reduce the effectiveness of DUI laws.

The Incidence and Timing of Treatment-Requiring Retinopathy of Prematurity in Nanopremature and Micropremature Infants in the United States: A National Multicenter Retrospective Cohort Study.

PARTICIPANTS: This article includes 7293 infants (14 586 eyes) screened for ROP across 5 centers in the United States (Austin Retina Associates, Austin, TX; Bascom Palmer Eye Institute, Miami, FL; Beaumont Eye Institute, Royal Oak, MI; Massachusetts Eye and Ear, Boston, MA; and Stanford Byers Eye Institute, Stanford, CA). PURPOSE: To analyze the incidence and timing of treatment requiring retinopathy of prematurity (ROP) in extremely small premature infants. We hypothesize that the smaller the infant by gestational age and birthweight, the higher their likelihood of requiring treatment for ROP. DESIGN: Premature infants screened for Retinopathy of Prematurity from 2002-2022 were divided into cohorts based on the following criteria based on gestational age (GA) and birth weight (BW). "Micropremature infants" are infants born between 24-26 weeks GA and between 600-799 g BW. "Nanopremature infants" are born ≤ 24 weeks GA and ≤ 600 g BW. METHODS: Retrospective chart review. MAIN OUTCOME MEASURES: The incidence and timing of treatment-requiring ROP. RESULTS: We found that infants defined as nanopremature had a ∼63% chance of requiring treatment at an average postmenstrual age (PMA) of 36.6 weeks, whereas those defined as micropremature had a 30% chance of requiring treatment at an average PMA of 36.3 weeks. This significantly contrasts with the risk of all screened babies for ROP where the risk of requiring treatment was 8.5%. CONCLUSION: Micropremature and nanopremature infants are significantly more likely to require treatment for ROP. With demographic data matched to all 5 major US regions spanning the last decade, these results have the potential to inform neonatologists, pediatricians, and ophthalmologists of an important shift in the landscape of prematurity in the United States. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

A Literary Pediatric Retina Fellowship With Michael T. Trese, MD.

Michael T. Trese, MD (1946-2022), a vitreoretinal surgeon, made significant contributions to the field of retina. Although most known for his work in pediatric retina surgery, he was a pioneer in areas such as medical retina, translational research, and telemedicine. This article reviews his major contributions to spread his knowledge more widely to vitreoretinal trainees and specialists. We discuss six areas where Trese made a lasting impact: lens-sparing vitrectomy, familial exudative vitreoretinopathy, congenital X-linked retinoschisis, autologous plasmin enzyme, regenerative medicine, and telemedicine. [Ophthalmic Surg Lasers Imaging Retina 2023;54:701-712.].

Genetic analysis and multimodal imaging identify novel mtDNA 12148T>C leading to multisystem dysfunction with tissue-specific heteroplasmy.

Patients with mitochondrial disorders present with clinically diverse symptoms, largely driven by heterogeneous mutations in mitochondrial-encoded and nuclear-encoded mitochondrial genes. These mutations ultimately lead to complex biochemical disorders with a myriad of clinical manifestations, often accumulating during childhood on into adulthood, contributing to life-altering and sometimes fatal events. It is therefore important to diagnose and characterize the associated disorders for each mitochondrial mutation as early as possible since medical management might be able to improve the quality and longevity of life in mitochondrial disease patients. Here we identify a novel mitochondrial variant in a mitochondrial transfer RNA for histidine (mt-tRNA-his) [m.12148T>C], that is associated with the development of ocular, aural, neurological, renal, and muscular dysfunctions. We provide a detailed account of a family harboring this mutation, as well as the molecular underpinnings contributing to cellular and mitochondrial dysfunction. In conclusion, this investigation provides clinical, biochemical, and morphological evidence of the pathogenicity of m.12148T>C. We highlight the importance of multiple tissue testing and in vitro disease modeling in diagnosing mitochondrial disease.

Telemedicine retinopathy of prematurity severity score (TeleROP-SS) versus modified activity score (mROP-ActS) retrospective comparison in SUNDROP cohort.

Identifying and planning treatment for retinopathy of prematurity (ROP) using telemedicine is becoming increasingly ubiquitous, necessitating a grading system to help caretakers of at-risk infants gauge disease severity. The modified ROP Activity Scale (mROP-ActS) factors zone, stage, and plus disease into its scoring system, addressing the need for assessing ROP's totality of binocular burden via indirect ophthalmoscopy. However, there is an unmet need for an alternative score which could facilitate ROP identification and gauge disease improvement or deterioration specifically on photographic telemedicine exams. Here, we propose such a system (Telemedicine ROP Severity Score [TeleROP-SS]), which we have compared against the mROP-ActS. In our statistical analysis of 1568 exams, we saw that TeleROP-SS was able to return a score in all instances based on the gradings available from the retrospective SUNDROP cohort, while mROP-ActS obtained a score of 80.8% in right eyes and 81.1% in left eyes. For treatment-warranted ROP (TW-ROP), TeleROP-SS obtained a score of 100% and 95% in the right and left eyes respectively, while mROP-ActS obtained a score of 70% and 63% respectively. The TeleROP-SS score can identify disease improvement or deterioration on telemedicine exams, distinguish timepoints at which treatments can be given, and it has the adaptability to be modified as needed.

Viral-specific T cells for Cytomegalovirus retinitis following hematopoietic stem cell transplantation: A success story.

Cytomegalovirus retinitis (CMVR) following hematopoietic stem cell transplantation (HCT) for a primary immunodeficiency is a rare but highly morbid condition with potential irreversible consequences despite optimal antiviral pharmacotherapy. Viral-specific T cells (VSTs) pose a promising and safe approach eradicating intractable viral disease. We describe the case of a 21-month-old male with Wiskott-Aldrich syndrome (WAS) and CMVR post HCT with sustained long-term virologic and clinical response after CMV-specific T-cell therapy. This case highlights the need to consider VST as an adjunct upfront strategy in refractory CMVR and for routine ophthalmologic screening and surveillance in high-risk patients post HCT.

Cellular and subcellular optogenetic approaches towards neuroprotection and vision restoration.

Optogenetics is defined as the combination of genetic and optical methods to induce or inhibit well-defined events in isolated cells, tissues, or animals. While optogenetics within ophthalmology has been primarily applied towards treating inherited retinal disease, there are a myriad of other applications that hold great promise for a variety of eye diseases including cellular regeneration, modulation of mitochondria and metabolism, regulation of intraocular pressure, and pain control. Supported by primary data from the authors' work with in vitro and in vivo applications, we introduce a novel approach to metabolic regulation, Opsins to Restore Cellular ATP (ORCA). We review the fundamental constructs for ophthalmic optogenetics, present current therapeutic approaches and clinical trials, and discuss the future of subcellular and signaling pathway applications for neuroprotection and vision restoration.

Time to Treatment of Pediatric Retinal Detachments: A US Claims-based Analysis.

PURPOSE: To characterize delays in diagnosis and treatment of retinal detachments (RDs) in a pediatric population. DESIGN: Retrospective cohort study using insurance claims data. SUBJECTS: Pediatric patients with RD who underwent repair in the outpatient setting. METHODS: A retrospective analysis of commercially insured patients from a national cohort (IBM MarketScan Research Databases) aged ≤ 18 years with an incident diagnosis of RD between 2007 and 2016. Patients with preceding eye-related visits, time to diagnosis, and time to repair were calculated and compared between patients with pre-existing ocular diagnosis and those without. MAIN OUTCOME MEASURES: The time from diagnosis to specialist consultation, time from diagnosis to repair, time from specialist consultation to repair, number of preceding visits, and presence of previous eye-related diagnosis. RESULTS: Our sample consisted of 826 patients, the majority (77%) of whom were diagnosed with rhegmatogenous RD. Only 40% of patients had at least 1 preceding eye-related visit, and 33% had at least 2 visits before RD diagnosis, with a median time from the last eye-related visit of 32 days (4-197 days) and median time from the second to last visit of 118 days (24-437 days). The median time from RD diagnosis to repair was 2 days (0-9 days). The 323 (37.9%) patients with pre-existing ocular diagnoses more frequently had at least 1 (44% vs. 37%; P = 0.079) or 2 preceding eye-related visits (40% vs. 29%; P = 0.002) compared with those without and also had a shorter time to RD diagnosis (median, 14.5 days vs. 44.5 days; P = 0.011) and repair (1 day vs. 3 days; P = 0.003). CONCLUSIONS: Retinal detachment is an important cause of morbidity in children. This work highlighted how pediatric patients without previous ocular diagnoses and visits with eye care professional may have a delayed diagnosis and repair of their RD. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Systemic and Intraocular Methotrexate for the Prevention and Treatment of Proliferative Vitreoretinopathy in Children With Rhegmatogenous Retinal Detachment and Underlying Inflammatory Disease.

Purpose: This index study highlights the efficacy and safety of a combined surgical and medical therapy (with intraocular and systemic methotrexate) of pediatric rhegmatogenous retinal detachments (RRD) complicated by proliferative vitreoretinopathy (PVR). Methods: Three pediatric patients with RRD complicated by PVR in the setting of underlying atopic dermatitis and/or uveitis who were treated with a combination of vitreoretinal surgery and intraoperative intravitreal methotrexate (MTX) (40mg) infusion, followed by at least one injection of 200 µg of MTX into the silicone oil-filled vitreous cavity, are reported. In addition, the patients received short-term systemic immunosuppression with systemic (oral or subcutaneous 20 mg weekly MTX for 12 weeks) and/or steroids. Results: Retinal reattachment with improvement in visual acuity was achieved in all eyes following a single surgery and remained to the final follow-up examination after oil removal. There were no observed side effects of intraocular or systemic MTX. Conclusions: The safety and efficacy of this combination therapy suggests that it could be a successful strategy for treating pediatric patients with RRD with or without PVR in the presence or absence of underlying inflammatory diseases.

REPRODUCTIVE OPHTHALMOLOGY: The Intersection of Inherited Eye Diseases and Reproductive Technologies.

PURPOSE: To propose a working framework for patients with inherited eye diseases presenting to ophthalmologists who are interested in assisted reproductive technology and preimplantation genetic testing. METHODS: Retrospective chart review and case series of three families with inherited eye diseases who successfully underwent preimplantation genetic testing, in vitro fertilization, and birth of unaffected children. RESULTS: Preimplantation genetic testing was performed for three families with different inherited eye diseases, which included autosomal dominant retinitis pigmentosa, autosomal recessive achromatopsia, and X-linked Goltz syndrome. Preimplantation genetic testing led to the identification of unaffected embryos, which were then selected for in vitro fertilization and resulted in the birth of unaffected children. CONCLUSION: A close collaboration between patients, families, ophthalmologists, reproductive genetic counselors, and reproductive endocrinology and infertility specialists is the ideal model for taking care of patients interested in preimplantation genetic testing for preventing the transmission of inherited eye diseases.

CRB1-associated retinal dystrophy presenting as self-resolving opsoclonus and posterior uveitis.

PURPOSE: To describe the unusual case of inflammatory CRB1-associated retinal dystrophy that initially presented with self-resolving opsoclonus. OBSERVATIONS: We report the case of a now 2-year-old female who developed opsoclonus without myoclonus at the age of 4 months. An extensive workup for neuroblastoma and other systemic diseases was unremarkable, and all unusual eye movements self-resolved at age 10 months. Twenty-one months after initial presentation, she began having reduced visual behaviors, and comprehensive ophthalmic exam at that time revealed recurrent saccadic intrusions as well as severe, chronic retinal inflammation and dystrophic changes. An extensive infectious and inflammatory workup was negative. Genetic sequencing revealed two variants in CRB1: a heterozygous missense mutation and a heterozygous novel deletion involving exon 12. The patient was treated with monthly infliximab and methylprednisolone infusions with improvement in her optic disc and macular capillary leakage. The patient's 8-month-old sister also harbored the same variants in CRB1 and had early signs of retinal dystrophy and peripheral vascular leakage on exam. CONCLUSION: Saccadic intrusions may be the first sign of a retinal dystrophy, and infants and children with this presentation should undergo a complete eye exam. We further highlight the link between CRB1-associated retinal dystrophy and inflammation, and how systemic steroids and tumor necrosis factor alpha (TNF-α) inhibitors may be effective therapies. Finally, we report a novel deletion in CRB1 that is likely highly penetrant.

Referable Macular Hemorrhage-A Clinically Meaningful Screening Target in Newborn Infants. Position Statement of the Association of Pediatric Retina Surgeons.

Universal newborn eye screening facilitates early diagnosis of ocular abnormalities and mitigates vision loss. "Referral warranted" eye disease is present at birth in about 5.5% of term infants, with "macular hemorrhage impinging on the fovea" representing about 50% of referral warranted disease. The Association of Pediatric Retina Surgeons held a symposium on February 9, 2021 that culminated in a position statement on "referable macular hemorrhage" (RMH) in newborn infants. RMH is meaningful in that in can cause amblyopia through deprivation, can be readily captured with wide-angle photography in a safe and efficient manner, and may lead to early intervention with mitigation of vision loss. [Ophthalmic Surg Lasers Imaging Retina. 2022;53:3-6.].

Incidence and Visual Outcomes of Endophthalmitis After Intravitreal Injection of Dexamethasone Implant vs Ranibizumab.

Purpose: To compare the incidence and visual outcomes of endophthalmitis after injection of an intravitreal dexamethasone implant and injection of intravitreal ranibizumab. Methods: This retrospective cohort study assessed endophthalmitis in eyes receiving an intravitreal injection of a 0.7 mg dexamethasone implant (DEX group), 0.5 mg ranibizumab (R5 group), or 0.3 mg ranibizumab (R3 group) between January 1, 2016, and May 31, 2018, at 2 large retina practices in the United States. Results: Suspected endophthalmitis occurred in 5 eyes after 4973 DEX injections, 43 eyes after 163 974 R5 injections, and 6 eyes after 18 954 R3 injections. Suspected endophthalmitis was significantly more common in the DEX group (1/995) than in the R5 group (1/3813) (P = .008) but not than in the R3 group (1/3159) (P = .10). Visual acuity outcomes were similar in the 3 groups. Conclusions: Suspected endophthalmitis might be more common after 0.7 mg dexamethasone injections than after 0.5 mg ranibizumab injections. Culture-positive endophthalmitis rates were similar across all 3 medications.

Management of Type 2 Retinopathy of Prematurity or Less in Infants Aged 45 Weeks Postmenstrual Age or Older.

BACKGROUND AND OBJECTIVE: This study aimed to identify the degree of concordance between fluorescein angiograms (FA) and fundus photographs (FP) in assessing the severity and potential need for treatment in infants 45 weeks or older postmenstrual age (PMA) with type 2 or less retinopathy of prematurity (ROP). PATIENTS AND METHODS: An observational retrospective case series performed at Associated Retinal Consultants, William Beaumont Hospital in Royal Oak, Michigan. All infants born between 2006 and 2016 with stage 1 to 3 ROP that did not meet type 1 ROP criteria (type 2 or less) who received ablative laser therapy during or after age 45 weeks PMA. Pretreatment FP and FA images were randomized and sent to nine expert retina specialist graders to assess severity and inter-grader variability. RESULTS: A total of 10 babies (19 eyes) were enrolled in this study, and 53 FAs and 27 FPs of these 19 eyes were selected to be interpreted by the nine graders. The number of eyes deemed to be abnormal and warranted for treatment was higher with FA, whereas more eyes were deemed "normal" with FP. CONCLUSION: Although still controversial, knowledge of these findings may encourage retina specialists to closely examine infants with mild ROP older than age 45 weeks PMA and consider ablative laser therapy under certain conditions (even if not meeting type 1 Early Treatment for ROP criteria). [Ophthalmic Surg Lasers Imaging Retina. 2021;52:636-641.].

The Present and Future of Mitochondrial-Based Therapeutics for Eye Disease.

Translational Relevance: Mitochondria are viable therapeutic targets for a broad spectrum of ocular diseases.

80 Years of vision: preventing blindness from retinopathy of prematurity.

Retinopathy of prematurity (ROP) is one of the leading yet preventable causes of childhood blindness worldwide. The purpose of this review is to provide a practical template for observational and treatment methods in order to reduce the overall incidence of any ROP and to improve both short-term and long-term outcomes once Type 1 ROP (treatable ROP) develops.