The 200-Year Timeline on Botulinum Toxin: From Biologic Poison to Wonder Drug.

The history of botulinum toxin dates back to the late 1700s, when food preparation, storage, and later canning practices led to outbreaks of botulism across Europe and the United States. It is from these initial incidents that the remarkable discovery of botulinum toxin was eventually made, sparking over 200 years of further scientific inquiry and medical innovation. To date, 6 botulinum toxin products have been commercialized in North America with numerous indications across the specialties of ophthalmology, neurology, urology, dermatology, plastic surgery, and otolaryngology. This article traces the key moments and important players in the remarkable journey of this biologic poison and wonder drug. J Drugs Dermatol. 2024;23(1) doi:10.36849/JDD.7288.

Type 4 Duane syndrome.

PURPOSE: To identify cases of synergistic divergence whose characteristics suggest that this entity is a form of Duane syndrome. METHODS: The records of all patients with a Duane syndrome diagnosis, including standardized eye position photographs, from the E-Consultation program of Cybersight, Orbis International were analyzed. RESULTS: A total of 350 Duane syndrome cases were identified. Of these, 19 (5%) had features consistent with synergistic divergence, or type 4 Duane syndrome. Of the 19, 16 (84%) were male, 15 (79%) had palpebral fissure narrowing, all had anomalous head posture, and 18 (95%) were exotropic. Only 9 (47%) patients were reported to have undergone surgery. CONCLUSIONS: Synergistic divergence is a rare entity with features similar to those of Duane syndrome. We suggest that this entity be classified as type 4 Duane syndrome, because it has unique findings and an innervation pattern that differs from the other 3 recognized types.

Telemedicine for retinal care in developing nations: the ORBIS Cyber-Sight programme, 2003-2011.

ORBIS International has provided a web-based ophthalmic disease consultation service, Cyber-Sight, for developing nations since 2003. The system connects partner physicians with mentor physicians. We have reviewed consultations concerning retinal cases submitted from June 2003 to December 2011. Of 943 retinal consultations reviewed, 117 were excluded, mainly for reasons of technical limitations at the partner sites. Of the 826 included cases, 504 patients were male and 322 were female. The average age of the patients was 43 years (range 2 months to 86 years). Cases were submitted from partner physicians in 30 countries, with five countries accounting for 82% of the cases (India, Vietnam, Indonesia, China, Jordan). There was a rise in the case submission rate to a peak of 251 cases in 2010. The mean consultant response time was 5 days (SD 9). The mean time to case closure was 19 days (SD 92). The most common diagnoses were diabetic retinopathy (n = 101), retinal vascular occlusion (n = 75) and retinal detachment (n = 61). The working diagnosis submitted by the partner did not match the mentor's diagnosis in 153 cases (19%). The number of incorrect initial partner diagnoses demonstrates that the teleretinal programme serves a useful diagnostic role for partner physicians. The Cyber-Sight programme is a viable method of delivering advanced retinal expertise to partner institutions and increasing capacity for partner doctors in the developing world.

Surgical results in the management of advanced primary congenital glaucoma in a rural pediatric population.

OBJECTIVE: To present the anatomic and functional results of surgical treatment for advanced primary congenital glaucoma (PCG) in a rural setting. DESIGN: Retrospective, observational case series. PARTICIPANTS: Forty eyes of 22 consecutive patients diagnosed with PCG and who underwent surgical treatment. METHODS: All eyes underwent surgical treatment for PCG. Type of surgery and postoperative complications were noted. We examined anatomic and functional indices before and after the operation. MAIN OUTCOME MEASURES: Visual acuity (VA), intraocular pressure (IOP), refractive spherical error, cup-to-disc ratio (CDR), and horizontal corneal diameter (HCD). RESULTS: Average age at the time of surgery was 3.3 years (range, 0.4-10) and the mean follow-up was 6 months (range, 1-11). 15% showed marked lens dislocation owing to the severe buphthalmos at presentation. Preoperative IOP was 54 ± 2 mmHg, HCD was 15.1 ± 0.3 mm, and CDR (when visible) was 0.8 ± 0.02. Surgical intervention included 31 trabeculotomies, 6 Ahmed Glaucoma Valve implants, 1 goniotomy, and 2 eviscerations. Serious complications were noted in 4 eyes. Final postoperative IOP was 23 ± 2 mmHg (P < 0.0001). Patients were significantly more likely to have ambulatory VA (following objects or better) after operation (18% vs 64%; P < 0.0001). CONCLUSIONS: Our surgical outcomes in children with advanced PCG demonstrated moderate overall improvement in IOP and modest improvement of VA. Deep deprivation amblyopia, severe disease manifestation at presentation, opaque corneas, and frequent lens dislocation limited the possible success. These data further signify the need for effective, timely screening of children and prompt recognition by health care workers to reduce the rate of avoidable blindness in developing countries.

Bilateral primary congenital glaucoma in monozygotic twins.

Primary congenital glaucoma is an uncommon pediatric ocular disease contributing to a disproportionately high percentage of childhood blindness worldwide. This case report describes bilateral primary congenital glaucoma in monozygotic twins who first presented to an ophthalmologist in Ethiopia at 6 years of age. Both had severe, protracted disease, with only moderate improvement after surgical intervention.

Development of retinoblastoma programs in Central America.

BACKGROUND: Retinoblastoma, a curable eye tumor, is associated with poor survival in Central America (CA). To develop a retinoblastoma program in El Salvador, Guatemala, and Honduras, twinning initiatives were undertaken between local pediatric oncology centers, nonprofit foundations, St. Jude Children's Research Hospital, and the University of Tennessee Hamilton Eye Institute. PROCEDURE: The retinoblastoma program focused on developing early diagnosis programs in Honduras with national vaccination campaigns, developing treatment protocols suited to local conditions, building local networks of oncologists and ophthalmologists, training local healthcare providers, using modern donated equipment for diagnosis and treatment, and the ORBIS Cybersight consultation program and Internet meetings to further education and share expertise. Pediatric ophthalmologists and oncologists worked with foundations to treat patients locally with donated equipment and Internet consultations, or at the center in Guatemala. RESULTS: Number of patients successfully treated increased after the program was introduced. For 2000-2003 and 2004-2007, patients abandoning/refusing treatment decreased in Guatemala from 20 of 95 (21%) to 14 of 123 (11%) and in Honduras from 13 of 37 (35%) to 7 of 37 (19%). Survival in El Salvador was good and abandonment/refusal low for both periods. Of 18 patients receiving focal therapy for advanced disease, 14 have single remaining eyes. CONCLUSION: Development of the program in CA has decreased abandonment/refusal and enabled ophthalmologists at local centers to use modern equipment to provide better treatment. This approach might serve as a guide for developing other multispecialty programs.

Retinoblastoma: one world, one vision.

Retinoblastoma is curable when diagnosed early and treated appropriately; however, the prognosis is dismal when the basic elements of diagnosis and treatment are lacking. In developing countries, poor education, lower socioeconomic conditions, and inefficient health care systems result in delayed diagnosis and suboptimal care. Furthermore, the complexity of multidisciplinary care required is seldom possible. Whereas ocular salvage is a priority in the Western world, death from retinoblastoma is still a major problem in developing countries. To bring the 2 ends of this spectrum together and provide a forum for discussion, the "One World, One Vision" symposium was organized, at which clinicians and researchers from various cultural, geographic, and socioeconomic backgrounds converged to discuss their experiences. Strategies for early diagnosis in developing countries were discussed. Elements of the development of retinoblastoma centers in developing countries were discussed, and examples of successful programs were highlighted. An important component in this process is twinning between centers in developing countries and mentor institutions in high-income countries. Global initiatives by nongovernmental organizations such as the International Network for Cancer Treatment and Research, Orbis International, and the International Agency for Prevention of Blindness were presented. Treatment of retinoblastoma in developing countries remains a challenge; however, it is possible to coordinate efforts at multiple levels, including public administrations and nonprofit organizations, to improve the diagnosis and treatment of retinoblastoma and to improve the outcome for these children.

Diagnosis and management of strabismus using telemedicine.

This study was undertaken to measure the effect of telemedicine consultation for diagnosis and treatment planning in cases of strabismus. Telemedicine consultation records of all patients on ORBIS Telemedicine Cyber-Sight that resulted in a final diagnosis of superior oblique palsy (SOP), Duane syndrome (DS), and Brown syndrome (BS) were collected. The following were then determined: (1) the clinical characteristics of patients in each category, (2) the diagnosis submitted by the doctor requesting consultation compared to the diagnosis determined by the mentor, and (3) the treatment plan submitted with the consultation request compared to the mentor's suggested plan. The clinical characteristics of patients with SOP, DS, and BS were similar to those reported in the literature. There were 89 with SOP, 131 with DS, and 50 with BS. Partners and mentors agreed on the diagnosis of SOP in 81% of cases, DS in 79% of cases, and BS in 72% of cases. Mentors agreed with the partners' proposed treatment plan in SOP 35%, DS 55%, and BS 52%. Mentors are likely to change the diagnosis proposed by doctors seeking consultation for strabismus in 25% of cases and provide a new treatment plan in more than 50% of cases. The clinical characteristics of those strabismus entities selected matched those found in the literature, making it likely that the cases as viewed on telemedicine presented a true clinical picture.

Use of telemedicine to assist ophthalmologists in developing countries for the diagnosis and management of four categories of ophthalmic pathology.

INTRODUCTION: The diagnosis and treatment plans proposed by ORBIS Telemedicine partners, all of whom were ophthalmologists, via Cyber-Sight, in four ophthalmic sub-specialty categories were compared to those suggested by expert mentors. METHODS: Records of referrals of patients via Cyber-Sight to mentors with a diagnosis of: glaucoma, pediatric cataract, external disease, and disorders related to the ocular adnexa requiring oculo-plastic treatment were reviewed. Records recalled from the Cyber-Sight electronic archives included: medical history, images of clinical findings, partner diagnosis, partner treatment plan, mentor diagnosis, and mentor treatment plan. Partners' diagnosis and treatment plans were compared to those of the mentors. Based on results of prior studies, mentor opinions were those considered valid (Helveston et al 2001). RESULTS: A total of 135 cases were reviewed: 70 external disease, 42 oculo-plastics, 16 glaucoma, and 7 pediatric cataract. The partner's diagnosis agreed with that of the mentor in: glaucoma 81%, pediatric cataract 86%, external disease 76%, and oculo-plastics 86%. Partners were considered to have suggested the correct treatment plan in: glaucoma 56%, pediatric cataract 71%, external disease 70%, and oculo-plastics 60%. Mentors provided additional comments and suggestions for further study in more than three-quarters of the cases. DISCUSSION: If one considers that the mentors are correct in each case, they offered a different diagnosis in 18% of cases. For treatment, mentors offered an alternate plan in more than a quarter of cases. The basis for considering the mentors being more accurate in diagnosis and treatment planning after viewing pictures and reading history than the partners who actually saw and examined the patients is based on personal experience of the authors. This includes a study done by one of them (EMH) demonstrating that experts when asked to view cases presented via telemedicine agreed nearly 100% on diagnosis and by a like amount on the method of treatment. In addition to this, results of this present study are similar to those for strabismus; a condition that was studied earlier (Helveston et al 2001). Still to be determined is whether this type of consultation changes outcome of treatment.

Visual training: current status in ophthalmology.

PURPOSE: To inform ophthalmologists of the current status of visual training. DESIGN: Personal perspective. METHOD: A perspective and analysis of current practices that include a review of the literature and personal experiences of the author. RESULTS: Visual training of some sort has been used for centuries. In the first half of the twentieth century, in cooperation with ophthalmologists, orthoptists introduced a wide variety of training techniques that were designed primarily to improve binocular function. In the second half of the twentieth century, visual training activities were taken up by optometrists and paramedical personnel to treat conditions that ranged from uncomfortable vision to poor reading or academic performance. Other visual training has been aimed at the elimination of a wide variety of systemic symptoms and for the specific improvement of sight and even for the improvement of athletic performance. At present, ophthalmologists and orthoptists use visual training to a very limited degree. Most visual training is now done by optometrists and others who say it works. Based on an assessment of claims and a study of published data, the consensus of ophthalmologists regarding visual training is that, except for near point of convergence exercises, visual training lacks documented evidence of effectiveness. CONCLUSION: Although visual training has been used for several centuries, it plays a minor and actually decreasing role in eye therapy used by the ophthalmologist. At the beginning of the twenty-first century, most visual training is carried out by non-ophthalmologists and is neither practiced nor endorsed in its broadest sense by ophthalmology.

Treatment of upshoot and downshoot in Duane syndrome by recession and Y-splitting of the lateral rectus muscle.

BACKGROUND: Duane syndrome is characterized by abduction deficiency, narrowing of the palpebral fissure with retraction of globe on attempted adduction, and upshoot or downshoot, which can be the most prominent feature of the motility disorder. The upshoot and downshoot is believed to be caused by a tautness or leash effect from the lateral rectus muscle. The purpose of this study was to present the results of recession of the lateral rectus muscle with Y-splitting in the treatment of upshoot and downshoot in Duane syndrome. METHODS: Ten patients with Duane syndrome underwent surgery for severe upshoot or downshoot. Lateral rectus muscles recession from 5.0 to 9.0 mm and Y-splitting was accomplished in all patients. In 6 patients, the medial rectus muscles were recessed simultaneously from 5.0 to 6.0 mm to correct the associated marked globe retraction and ocular deviation. RESULTS: Mean age at the time of surgery was 9.9 +/- 6.9 years (range, 3 to 20). Median follow up was 6 months (range, 3 weeks to 3 years). After surgery, all patients showed a marked decrease in upshoot or downshoot as well as improvement in globe retraction and face turn, where present. CONCLUSIONS: Recession of lateral rectus muscle with Y-splitting is an extremely effective procedure in the treatment of significant upshoot and downshoot associated with globe retraction in Duane syndrome. When combined with simultaneous recession of the medial rectus muscle, it improves globe retraction and corrects ocular deviation.